[68Ga]Ga-FAPI PET/CT for Response Evaluation During Immune Checkpoint Inhibitor Therapy in Malignant Melanoma
Phase: PHASE2
Conditions: Malignant Melanoma Stage IV
Sponsor: Barbara Malene Fischer

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BEFAST STUDY: 
[68Ga]Ga-FAPI total body PET/CT for Better and Faster 
imaging in cancer 
Protocol: [68Ga]Ga-FAPI PET/CT for response evaluation during 
immune checkpoint inhibitor therapy in malignant melanoma 

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General Information 
EudraCT information: 
EU trial number: 2023-509549-11-00 
Sponsors protocol number: 4 
Study protocol version: 4 
Sponsor 
Barbara Malene Fischer, MD., PhD., dr. med 
Deputy Chief Executive, Research Director 
Copenhagen University Hospital, Rigshospitalet, section 1141 
Blegdamsvej 9, DK-2100 Copenhagen 
Principal Investigator (PI): 
The information of the current PI is available on the European clinical trial information system (CTIS) 
website: https://euclinicaltrials.eu/. Information on this trial can be retrieved by using the EU trial number 
(2023-509549-11-00) as a search criteria. 
List of advisors: 
Inge Marie Svane, MD., PhD. 
Professor, Chief Physician 
Dept. of Oncology, National Center of Cancer Immune Therapy (CCIT-DK) 
Herlev Hospital 
inge.marie.svane@regionh.dk 
Helle Hendel, MD., PhD. 
Chef Physician 
Dept. of Nuclear Medicine, 
Herlev Hospital 
helle.hendel@regionh.dk 
Annika Loft, MD, PhD 
Chief Physician 
Dept. Clinical Physiology and Nuclear Medicine 
Copenhagen University Hospital, Rigshospitalet 
annika.loft.jakobsen@regionh.dk 
Ramune Aleksyniene, MD, PhD 
Chief Physician 
Dept. of Clinical Physiology and Nuclear Medicine 
Copenhagen University Hospital, Rigshospitalet 
ramune.aleksyniene@regionh.dk 
Flemming Littrup Andersen, MSc, PhD 
Chief Data Manager 

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Dept. Clinical Physiology and Nuclear Medicine, section 3982 
Copenhagen University Hospital, Rigshospitalet 
flemming.andersen@regionh.dk 
Jacob Madsen, MSc, PhD 
Chief Production Manager 
Cyclotron and Radiochemistry, section 3982, Dept. of Clinical Physiology and Nuclear Medicine 
Copenhagen University Hospital, Rigshospitalet 
jacob.madsen@regionh.dk 
Nicholas Mathew Gillings, MSc, PhD 
Chief Chemist, Qualified Person 
Cyclotron and Radiochemistry, section 3982, Dept. of Clinical Physiology and Nuclear Medicine 
Copenhagen University Hospital, Rigshospitalet 
nicholas.mathew.gillings@regionh.dk 
Localization of the trial: 
The localization of the trial is available at the CTIS website: https://euclinicaltrials.eu/. Information on this 
trial can be retrieved by using the EU trial number (2023-509549-11-00) as a search criteria. 
Collaborating departments 
Dept. of Clinical Physiology and Nuclear Medicine, Cyclotron section and Radiochemistry 
Copenhagen University Hospital, Rigshospitalet 
Phone number: 35453545 
Blegdamsvej 9, 2100 København Ø 
Denmark 
Department of Clinical Biochemistry Research Section 
Copenhagen University Hospital, Rigshospitalet 
Phone number: 35453545 
Blegdamsvej 9, 2100 København Ø 
Denmark 
Dept. of Oncology 
Dept. of Nuclear Medicine 
Herlev Hospital 
Phone number: 38683868 
Borgmester Ib Juuls Vej 1, 2730 Herlev 
Denmark 
Nordic Bioscience A/S 
Business Reg. (CVR): 30799968 
Phone number: +45 4452 5252 
Herlev Hovedgade 205; 2730 Herlev 

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___________________ 
GCP-monitoring: 
The GCP-unit of Copenhagen University Hospital will monitor the trial. 
GCP-unit, Copenhagen University Hospital 
Nordre Fasanvej 57, Skadestuevej 1, parterre 
2000 Frederiksberg 
Phone Number: 38635622 
Statement: 
The presented trials will be conducted in accordance with the protocol and laws and regulations on clinical 
trials provided by the Danish state and the European Union. 
Timeframe: 
The inclusion of patients is expected to start in the spring of 2025, and inclusion period is expected to last 
for 1 year. All patients have a follow-up period of 6 months. The trial will end 6 months after the last 
participant has completed their second [68Ga]Ga-FAPI-46 PET/CT. Data will be stored for 25 years. 
Signature 
Date: 
Sponsor’s/PI’s signature: 

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Glossary of Abbreviations 
Abbreviation 
Definition 
ICT 
immune checkpoint inhibitor therapy 
IrAE 
immune-related adverse events 
PET 
Positron Emission Tomography 
CT 
Computed Tomography 
[18F]FDG 
2-[18F]fluoro-2-deoxy-D-glucose (chemical name) 
FAP 
Fibroblast Activation Protein 
FAPI 
Fibroblast Activation Protein inhibitor 
[68Ga] 
Gallium-68 
[68Ga]Ga-FAPI-46 
[68Ga]gallium (S)-2,2',2''-(10-(2-(4-(3-((4-(2-(2-cyano-4,4-difluoropyrrolidin-1- 
yl)-2-oxoethylcarbamoyl)-quinolin-6-yl)(methyl)amino)-propyl)piperazin-1- 
yl)-2-oxoethyl) 1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetic acid 
(chemical name) 
TME 
Tumor microenvironment 
TNM 
Tumor, Node, Metastasis 
CAF 
Cancer Associated Fibroblasts 
mSv 
Millisievert 
mBq 
Megabecquerel 
ECM 
extra-cellular matrix 
MMP 
Matrix metalloprotease 
ELISA 
enzyme-linked immunosorbent assay 
CRF/eCRF 
Case Report Form/Electronic Case Report Form 
PI 
Principal Investigator 
IMPD 
Investigational medicinal product dossier 
SUV 
Standardized Uptake Value 
CTIS 
Clinical Trial information System 
AE 
Adverse Event 
AR 
Adverse Reaction 
SAE 
Serious Adverse Event 
SAR 
Serious Adverse Reaction 
SUSAR 
Suspected unexpected serious Adverse Reaction 
RECIST 
Response Evaluation Criteria in Solid Tumors 
RSI 
Reference safety information 
GCP-unit 
Good Clinical Practice-unit 
ICH-GCP 
International Conference on Harmonisation-Good Clinical Practice 

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Index 
General Information ........................................................................................................................................... 2 
EudraCT information ....................................................................................................................................... 2 
Sponsor ........................................................................................................................................................... 2 
Principal Investigator (PI) ................................................................................................................................ 2 
List of advisors: ........................................................................................................................................... 2 
Localization of the trial ................................................................................................................................... 3 
Collaborating departments ......................................................................................................................... 3 
GCP-monitoring ........................................................................................................................................... 4 
Statement ................................................................................................................................................... 4 
Timeframe: .................................................................................................................................................. 4 
Signature ..................................................................................................................................................... 4 
Glossary of Abbreviations ................................................................................................................................... 5 
1. 
Purpose: ...................................................................................................................................................... 8 
2. 
Background ................................................................................................................................................. 8 
2.1 Evaluation of FAP-biomarkers in liquid biopsies ..................................................................................... 10 
3. 
Trial Objectives.......................................................................................................................................... 11 
3.1 Study Hypothesis ..................................................................................................................................... 11 
3.2 Primary objectives ................................................................................................................................... 11 
3.3 Secondary objectives .............................................................................................................................. 11 
3.4 Exploratory objectives: ............................................................................................................................ 12 
4. 
Methods and Design ................................................................................................................................. 12 
4.1 Study Design ........................................................................................................................................... 12 
4.2 Trial procedure ........................................................................................................................................ 13 
4.3 Test group ............................................................................................................................................... 13 
4.3.1 Inclusion criteria ............................................................................................................................... 13 
4.3.2 Exclusion criteria .............................................................................................................................. 13 
4.3.3 Withdrawal of participants: ............................................................................................................. 14 
4.3.4 Compensation for potential dropouts and excluded and withdrawn patients ................................ 14 
4.4 Recruitment of Patients .......................................................................................................................... 14 
4.5 [68Ga]Ga-FAPI-46 PET/CT scan ................................................................................................................. 14 
4.6 Standard imaging [18F]FDG PET/CT (Comparator) ................................................................................... 16 
4.7 Blood sample .......................................................................................................................................... 17 

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4.8 List of medicinal products ....................................................................................................................... 17 
4.8.1 Investigational medicinal products .................................................................................................. 17 
4.8.2 Comparator ...................................................................................................................................... 17 
4.9 Interpretation of project scans ............................................................................................................... 17 
4.10 Interpretation of clinical scans .............................................................................................................. 17 
4.11 Endpoint assessment: ........................................................................................................................... 18 
4.11.1 Primary Objectives ......................................................................................................................... 18 
4.11.2 Secondary objectives ..................................................................................................................... 18 
4.11.3 Exploratory objectives: ................................................................................................................... 18 
5. 
Statistics .................................................................................................................................................... 19 
5.1 Sample size: ............................................................................................................................................ 19 
5.2 Statistical analyses: ................................................................................................................................. 19 
6. 
Interim analysis ......................................................................................................................................... 20 
7. 
Side effects and Risks ................................................................................................................................ 20 
7.1 Side effects of the investigational medicinal product ............................................................................. 20 
7.2 Side effects of the comparator ............................................................................................................... 20 
7.3 Risks during the study ............................................................................................................................. 20 
7.4 Safety ...................................................................................................................................................... 21 
7.5 Registration of side effects and events .................................................................................................. 21 
8. 
Collection of biological material................................................................................................................ 23 
9. 
Data Management .................................................................................................................................... 23 
9.1 Respect for participants’ physical and mental integrity and right to privacy .......................................... 23 
9.2 Information from and interpretation of the [68Ga]Ga-FAPI-46 PET/CT scans: ........................................ 24 
9.3 Analysis of blood samples ....................................................................................................................... 24 
9.4 Information from the clinical record ....................................................................................................... 24 
9.5 Quality control and monitoring ............................................................................................................... 25 
10. 
Science and ethics ................................................................................................................................. 25 
10.1 Guidelines for participants’ information and written consent .............................................................. 26 
10.2 Written consent .................................................................................................................................... 26 
11. 
Publication of results ............................................................................................................................ 26 
12. 
Insurance ............................................................................................................................................... 27 
13. 
Timeframe of the trial ........................................................................................................................... 27 
14. 
Protocol Synopsis .................................................................................................................................. 28 

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EU trial number: ........................................................................................................................................ 28 
Rationale of the study ............................................................................................................................... 28 
Study hypothesis ....................................................................................................................................... 28 
Objectives and endpoints ......................................................................................................................... 28 
Trial Design and trial population ............................................................................................................... 29 
Intervention .............................................................................................................................................. 29 
Safety and risks ......................................................................................................................................... 30 
Ethics and data protection ........................................................................................................................ 30 
15. 
References ............................................................................................................................................ 30 
16. Appendix ..................................................................................................................................................... 33 
 
 
 
 
1. Purpose: 
The purpose of the study is to evaluate positron emission tomography/computed tomography (PET/CT) 
combined with the tracer [68Ga]Gallium (S)-2,2',2''-(10-(2-(4-(3-((4-(2-(2-cyano-4,4-difluoropyrrolidin-1-yl)- 
2-oxoethylcarbamoyl)-quinolin-6-yl)(methyl)amino)-propyl)piperazin-1-yl) 2-oxoethyl) 1,4,7,10- 
tetraazacyclododecane-1,4,7-triyl)triacetic acid ([68Ga]Ga-FAPI-46) for response evaluation during immune 
checkpoint inhibitor therapy (ICT) in patients with advanced stage malignant melanoma. 
 
2. Background: 
Malignant melanoma is one of the most common types of cancers in Denmark. The incidence is 5.7% for 
women and 6.6% for men, and has increased over the past 10 years (1). The cancer is highly aggressive and 
treatment resistant especially in advanced stages. The introduction of immunotherapy and especially 
immune checkpoint inhibitor therapy (ICT) have improved survival rates for malignant melanoma patients 
with advanced stages (2, 3). In addition, ICT has also proven to be useful in an adjuvant and neoadjuvant 
setting for patients with low stages(4). 
Immune checkpoint inhibitors stimulate the patient’s own immune system by blocking regulators that 
normally downregulate and fine-tune T-cell activation (5). Blocking these regulators cause the T-cells to 
recognize foreign cells such as cancer cells. The therapy causes an indirect effect on cancer cells by 
generating an immune response towards the malignant tumor with immune-cell infiltration followed by 
inflammation and cytotoxicity. This effect induces a different tumor response compared to chemotherapy 
(6). ICT can cause a delayed tumor-response, and the responses can be preceded by initial worsening 
(pseudo-progression) (7). A downside to ICT is the immune-related adverse events (IrAE). IrAEs result from 
inflammatory damage in healthy tissue. Blocking the naturally occurring regulation of T-cells generates 
overactive immune cells, which causes the autoimmune reaction in addition to the desired reaction 
towards cancer cells. Most common IrAEs are diarrhea, pruritus, rash, colitis vitiligo and endocrine IrAEs 

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such as thyroiditis and hypophysitis (7). It is estimated that IrAE will occur in 15-90% of patients treated 
with ICT. More severe events can occur in 15-30% of patients, depending on the type of ICT used (5). 
Positron emission tomography (PET) with the radioactive tracer 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) 
combined with computed tomography (CT) is a scanner modality that plays a key-role in staging, response 
evaluation and follow-up in malignant melanoma(8-11). The radioactive tracer is an isotope fluorine 18 (18F) 
bound to the glucose analogue 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG). Patients are injected with the 
tracer prior to the scan, and cells will take up the radioactive glucose analogue. The basis for imaging with 
[18F]FDG PET is the increased glucose uptake and metabolic trapping in cancer cells(12). The CT component 
helps to visualize the anatomical location of the increased metabolism (13). 
Even though [18F]FDG PET/CT is a sensitive diagnostic tool, it still lacks specificity in some settings; [18F]FDG 
PET/CT has limited specificity in discriminating between inflammation and cancer, which is due to an 
unspecific uptake of [18F]FDG in inflammatory and infectious processes(8). This pitfall is especially evident 
in response evaluation of malignant melanoma treated with ICTs, as the inflammatory damage on the 
malignant lesions and the IrAEs can be confused with progressive disease (7). 
 
In recent years, researchers have focused on developing diagnostic tracers that targets the tumor 
microenvironment (TME). The TME is composed of non-malignant cells and has been recognized as an 
important part of tumor development (14). Cancer associated fibroblasts (CAFs) are a group of hyperactive 
stromacells within the TME, which can promote inflammation, tumor growth, angiogenesis and drug 
resistance. In vitro and in vivo studies have shown that CAFs promote melanoma cell proliferation and 
invasion (15, 16). CAFs express a variety of targetable factors, including the transmembrane glycoprotein 
called fibroblast activation protein (FAP). FAP is a known marker for CAFs and is upregulated in 90% of 
epithelial neoplasms and malignant melanoma (17). The presence of FAP on CAFs is also associated with 
tumor growth and migration(14). The so-called FAPI is a specific enzyme inhibitor that binds to FAP on CAFs 
(18). FAPI can be combined with different radioactive components to create radioactive tracers for use in 
PET imaging. Especially FAPI-variants bound to gallium-68 ([68Ga]Ga-FAPI) have been evaluated. Unlike 
[18F]FDG, [68Ga]Ga-FAPI does not reflect characteristics of the tumor and inflammatory cells (increased 
glucose metabolism), but the pro-carcinogenic microenvironment with CAFs (16). 
PET/CT imaging with [68Ga]Ga-FAPI variants has shown high sensitivity in diagnosing primary tumor 
(estimated pooled sensitivity of 1.0), as well as distant metastasis (estimated pooled sensitivity of 0.93) in 
different cancer types(19). This tracer is unique as it offers low uptake in most normal tissue and high 
uptake in malignant lesions (20, 21), thus improving tumor-to-background-ratio (TBR) compared to 
standard [18F]FDG PET/CT. One case study demonstrated increased uptake of [68Ga]Ga-FAPI compared to 
[18F]FDG in metastatic lesions in a patient with malignant melanoma (22). Especially, the liver metastases 
had increased uptake and improved TBRs on [68Ga]Ga-FAPI PET compared to [18F]FDG PET. 
 
The potential of [18Ga]FAPI PET in detecting malignant lesions in malignant melanoma patients have 
primarily been demonstrated in case reports. Larger studies on the use of [68Ga]FAPI-46 PET or other FAPI 
tracer variants in malignant melanoma patients have not been identified in the peer reviewed literature. 
[68Ga]Ga-FAPI-PET could also play a potential role in response evaluation of ICT, as CAFs has been 
recognized as emerging key-players in immune regulation of the TME, promoting local 

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immunosuppression(23-25). Interestingly, normal stromal fibroblasts inhibit invasion of malignant 
melanoma by recruiting immune cells and studies have shown that melanoma cells secrete regulating 
factors, which transform normal fibroblasts into CAFs (15). [68Ga]Ga-FAPI PET has also been suggested as a 
modality to detect or predict side effects of ICT. FAP-expression is also seen in non-cancerous tissue during 
physiological and pathological processes such as inflammation and fibrosis. As such, one pilot study found 
[68Ga]Ga-FAPI PET to be potentially useful in detecting early signs of ICT-associated myocarditis(26). Case 
studies have also reported increased FAPI-uptake in organs with an inflammatory reaction caused by ICT 
such as immunotherapy-related thyroiditis(27) and immuno-therapy related polyarthritis(28). 
Imaging with [68Ga]Ga-FAPI offers several potential advantages for patient comfort and logistics. No fasting 
or any other preparation prior to [68Ga]Ga-FAPI PET imaging is required. In addition, preliminary studies 
suggest that imaging can be performed as early as 10 min post injection (29). Thus, [68Ga]Ga-FAPI-46 could 
improve logistics and patient comfort. Current PET/CT with [18F]FDG requires patients to fast for 4-6 hours 
and wait for 60 mins after tracer injection before scanning. This adds to the relatively complex logistics and 
patient stress associated with a [18F]FDG PET/CT scan. This is especially evident for patients with melanoma, 
who undergo repeated [18F]FDG PET/CT scans during treatment and during the surveillance period. With 
[68Ga]Ga-FAPI-46 the time a patient needs to spend at the hospital for a PET/CT scan could potentially be 
reduced from approx. 2 hours to 1 hour by moving from [18F]FDG-PET/CT to [68Ga]Ga-FAPI-46 PET/CT. 
[68Ga]Ga-FAPI PET/CT has proven to be safe, with no tracer-related adverse events in adult cancer patients 
with various diagnoses (30-33). More than 1000 patients have been scanned with this tracer without any 
other reporting of side effects. In addition, a recently published paper by Hirmas et al presented data on 
303 patients scanned with [68Ga]Ga-FAPI-46(34) .The effective radiation dose of different types of FAPI- 
ligands bound to 68Ga varies between 0.008-0.016 millisieverts (mSv)/megabecquerel(MBq), which is lower 
than the effective dose of the standard [18F]FDG, 0.020 mSv/MBq (35). 
For the variant [68Ga]Ga-FAPI-46, administration of 200 MBq will cause a total body effective radioactive 
dose of 1,56+/-0.26 mSV (30). 
Based on the current knowledge, we believe that the tracer [68Ga]Ga-FAPI-46 can improve PET/CT for 
response evaluation for patients with melanoma treated with ICT. Furthermore, it has the potential to 
improve logistics and patient comfort for these patients. We do not believe any other studies have 
evaluated the use of the tracer [68Ga]Ga-FAPI-46 in response evaluation during ICT in this patient group. 
2.1 Evaluation of FAP-biomarkers in liquid biopsies 
Expression of FAP has been shown to be involved in extra-cellular matrix (ECM) remodeling and 
fibrogenesis. Excessive ECM degradation, e.g., from matrix metalloprotease (MMP) mediated cleavage 
during tumor progression, results in protein fragments that are released into the circulation. These 
fragments can be assessed non-invasively as a liquid biopsy and quantified as a disease-biomarker. As FAP 
has been shown to cleave ECM components including type I and III collagen, it can be expected that 
fragments from these cleavages would appear in circulation (36). Zhang et al. have identified multiple 
potential FAP cleavage sites in various ECM-associated proteins, including 1069AGPSGAPGPA1078 on mouse 
type III collagen (37). 
Nordic Bioscience has developed a competitive enzyme-linked immunosorbent assay (ELISA) targeting 
fragments of the alpha-1 chain of human type III collagen. This fragment is generated by cleavage of the 

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alpha-1 chain between amino acid residues P1069 and A1070 (C3F (the human equivalent to the previously 
mentioned cleavage site on mouse type III collagen)) by FAP. As such, these fragments can serve as a 
biomarker of FAP activity in the ECM. 
Nordic bioscience has also confirmed the specificity of the ELISA assay to the FAP cleaved type III collagen. 
They have also measured the levels of C3F in a lung cancer cohort and compared the levels in patients with 
adenocarcinoma and squamous cell carcinoma to healthy subjects. In this cohort, the levels of C3F were 
elevated in the patients with lung cancer (data not published). 
As C3F reflects FAP activity, we expect that it would correlate to the quantification of signal detected from 
the FAPI-tracer on [68Ga]Ga-FAPI-46 PET/CT of patients with cancer. In this study, we plan on exploring this 
correlation and generate preliminary evidence, which can support this hypothesis. In the future, these 
liquid biopsies of FAP activity biomarkers could be a potential screening tool for selecting the right patients 
to receive a PET/CT scan and to provide a way to monitor the patients between PET/CT scans. 
 
3. Trial Objectives 
The aim of the study is to evaluate [68Ga]Ga-FAPI-46 PET/CT as a non-invasive diagnostic tool for response 
evaluation during ICT in patients with advanced stage malignant melanoma. 
3.1 Study Hypothesis 
- 
 [68Ga]Ga-FAPI-46 PET/CT can improve response evaluation in patients suffering from advanced 
stage malignant melanoma treated with ICT and potentially serve as a biomarker. 
3.2 Primary objectives 
1) Evaluate [68Ga]Ga-FAPI-46-uptake in malignant lesions on [68Ga]Ga-FAPI-46 PET/CT. 
2) Evaluate changes in [68Ga]Ga-FAPI-46-uptake in malignant lesions on [68Ga]Ga-FAPI-46 PET/CT 
during ICT. 
3) Compare the changes in malignant lesions on [68Ga]Ga-FAPI-46 PET/CT with changes on standard 
[18F]FDG PET/CT and clinical response during ICT. 
Changes in FAPI-uptake in both primary tumour and metastases between the baseline [68Ga]Ga-FAPI-46 
PET/CT and [68Ga]Ga-FAPI-46 PET/CT after 3 months of ICT will be estimated qualitatively. This will be 
compared with changes on a standard [18F]FDG PET/CT and the clinical response (please refer to section 4.9 
and 4.10). 
3.3 Secondary objectives 
1) Evaluate if changes in [68Ga]Ga-FAPI-46 uptake during ICT in healthy tissue can be used as a 
predictor of potential side effects. 
2) Compare changes on [68Ga]Ga-FAPI-46 PET/CT in healthy tissue with changes on standard [18F]FDG 
PET/CT. 
Differences in tracer-uptake in healthy tissue between the baseline [68Ga]Ga-FAPI-46 PET/CT and [68Ga]Ga- 
FAPI-46 PET/CT after 3 months of ICT treatment will be evaluated. These changes will be compared to any 
side effect that the patients may experience during ICT. The FAPI-uptake on [68Ga]Ga-FAPI-46 PET/CT will 

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also be compared to findings on the routine follow-up [18F]FDG PET/CT (please refer to section 4.9 and 
4.10). 
3.4 Exploratory objectives: 
1) Correlation between [68Ga]Ga-FAPI-46-uptake on [68Ga]Ga-FAPI-46 PET/CT and levels of FAP activity 
biomarkers in serum blood samples. 
2) Correlation between [68Ga]Ga-FAPI-46-uptake on [68Ga]Ga-FAPI-46 PET/CT and levels of other 
biomarkers (e.g. ECM remodeling biomarkers) in serum blood samples. 
3) Correlation between levels of biomarkers in serum blood samples and treatment outcome. 
Blood samples from the participants included will be analyzed by Nordic Bioscience. Results from this 
analysis will be correlated to the disease activity measured quantitatively on the [68Ga]Ga-FAPI-46 PET/CT. 
In addition, we will correlate results from the biomarker analysis with treatment outcome of 
immunotherapy after 6 months using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. 
 
4. Methods and Design: 
4.1 Study Design 
The study is a phase II nonrandomized clinical trial evaluating [68Ga]Ga-FAPI-46 PET/CT for response 
evaluation during ICT in patients with advanced stage malignant melanoma with visible target lesions on 
standard [18F]FDG PET/CT. The study will be regarded as a pilot study and include 20 patients. 
The included participants will undergo two scans in addition to their standard imaging (diagnostic [18F]FDG 
PET/CT). At baseline the patients will undergo a [68Ga]Ga-FAPI-46 PET/CT (the project scan). This will be 
performed before initiation of ICT. In addition to the scan, a blood sample will be collected prior to 
injection of the tracers. After 12 weeks of treatment, the participant will undergo the same project scan 
([68Ga]Ga-FAPI-46 PET/CT) and a second blood sample in addition to their standard imaging (diagnostic 
[18F]FDG PET/CT). Thus, participants will be included for 2 [68Ga]Ga-FAPI-46 PET/CT, two blood samples and 
passive follow-up for 6 months after the last [68Ga]Ga-FAPI-46 PET/CT scan. 
For details on procedure, dose and frequency of injection of the tracer during the PET/CT scan please refer 
to section 4.5. All eligible participants will receive the standard treatment and standard surveillance of their 
cancer, no matter their participation status. 

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4.2 Trial procedure 
 
 
 
 
 
 
4.3 Test group 
Patients with advanced stage malignant melanoma with visible lesions on [18F]FDG PET/CT referred for ICT 
at the Dept. of Oncology Herlev Hospital will be sought enrolled. The study will include 20 patients with two 
evaluable [68Ga]Ga-FAPI-46 PET/CT. 
4.3.1 Inclusion criteria 
1) Male or female, 18 years old 
2) Histological verified metastatic or locally advanced malignant melanoma 
3) Visible malignant lesions on [18F]FDG PET/CT or CT 
4) Subjects must be considered inoperable 
5) Subjects must be considered medically suitable for ICT  
6) Subjects must be able to read and understand the patient information in Danish to give informed 
consent 
4.3.2 Exclusion criteria 
1) Ocular or mucosal melanoma 
2) Other concurrent cancer disease 
3) Previous systemic oncological treatment with ICT 
4) Pregnancy or lactation 
5) Weight more than the maximum limit of a PET/CT-scanner bed (140 kg) 
6) History of allergic reaction due to compounds similar to the chemical composition of [68Ga]Ga-FAPI- 
46 
If the patient is fertile, the patient will be asked about potential pregnancy and a urinary pregnancy test will 
be performed before inclusion. If the patient is postmenopausal (defined by the Danish Medical Agency as 
having absence of menstruation in at least 12 months before inclusion (38)) or infertile due sterilisation no 
pregnancy test will be performed. The result of the pregnancy test will be documented in the electronic 
case report form (eCRF). The reason for not performing the pregnancy test will also be documented in the 
eCRF. 

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If the patient exhibits signs of severe allergic reaction after injection of the tracer, the patient will be 
excluded from the study. 
If the PET/CT scan reveals that the tracer has been injected subcutaneously, the patient will be excluded 
from the trial. 
4.3.3 Withdrawal of participants: 
Patients must be withdrawn from the trial if the following occurs: 
1) The participant withdraws his/hers consent. 
2) The participant does not start the planned treatment with ICT. 
3) The participant stops ICT before 3 months of treatment. 
4) The participant cannot go through with the first [68Ga]Ga-FAPI-46 PET/CT. 
5) The investigator decides to withdraw the participant, in case the investigator finds it necessary for 
the safety of the individual participant. 
All data on participants, including excluded and withdrawn participants will be stored for 25 years. 
Data on participants who are excluded or withdrawn before the first [68Ga]Ga-FAPI-46 PET/CT will not be 
used for the final analysis. However, the data will be used to document total amount of excluded and 
withdrawn participants and reasons for this. Participants who are excluded after they have undergone the 
first project scan [68Ga]Ga-FAPI-46 PET/CT will be used for specific analysis, however, not the comparative 
analysis between the first and second [68Ga]Ga-FAPI-46 PET/CT scan. 
Participants who are excluded or withdrawn after the project scan will be observed for adverse reaction 
and events during and after the scan the same way as patients, who are included. 
The study will be terminated by the sponsor/principal investigator (PI) in case of unexpected or 
unacceptable side effects. However, we do not expect to end the trial prematurely due to safety, as no 
serious adverse reaction or events have been reported in previous trials. 
4.3.4 Compensation for potential dropouts and excluded and withdrawn patients 
Only patients with evaluable [68Ga]Ga-FAPI-46 PET/CT scans are accounted for in the final sample size. 
Thus, patients excluded or withdrawn from the study before the project scans will be replaced until at total 
number of 20 patients with two evaluable [68Ga]Ga-FAPI-46 PET/CT are met. 
4.4 Recruitment of Patients 
The recruitment arrangements are described in the document “Recruitment arrangements” in part II of the 
application dossier. 
4.5 [68Ga]Ga-FAPI-46 PET/CT scan 
Information on production, preparation and handling of the tracer [68Ga]Ga-FAPI-46 is described in the 
investigational medicinal product dossier (IMPD). The tracer is produced and finalized for administration at 
the Dept. of Clinical Physiology and Nuclear Medicine, Cyclotron section and Radiochemistry, 
Rigshospitalet, who will comply with directions described in the IMPD. The precursor FAPI-46 acetat salt 
(GMP) (which is used to produce the tracer) is produced by the firm ABX in Dresden, Germany and 
delivered via SOFIE Bioscience. 

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[68Ga]Ga-FAPI-46 is a sterile solution for intravenous injection. All incoming raw materials will be registered 
and tested. For each synthesis raw materials used will be documented in a dedicated batch record ensuring 
full traceability. The investigational medicinal product (IMP) is accounted for in the “IMP accountability 
log”, where used IMPs as well as destructed IMPs are accounted for. Methods for quality control are 
validated. [68Ga]Ga-FAPI-46 will only be released when all quality control tests are within specifications. The 
released product will be accompanied with a dose sheet containing information about the batch number, 
the volume, the calibration time, and the available doses at different time points within the shelf-life of the 
product. Final release will be performed by a person qualified to do so by The Danish Medicines Agency 
(Qualified Person). The Dept. of Clinical Physiology and Nuclear Medicine will handle the bookkeeping 
regarding the use of the compound. The tracer has proven to be safe, and no adverse reactions have been 
reported (30-32). 
 
When the [68Ga]Ga-FAPI-46 is administered, the batch number, the injected/administered dose and the 
time of injection/administration will be documented on a PET administration sheet (“PET arbejdsseddel”), 
which is correlated to each individual participant with their CPR number. This sheet will be saved, which 
also will secure full traceability. Any excess tracer not administered to the subjects will be destroyed. 
Prior to initiation of ICT, participants will undergo an [68Ga]Ga-FAPI-46 PET/CT scan at the Department of 
Clinical Physiology and Nuclear Medicine, PET section 3982, Rigshospitalet. 
Upon arrival, the participant will be placed in a bed in a relaxed prone position. The participant will be 
informed about the outline of the scan, and questioned about relevant conditions (allergies, potential 
pregnancy etc.). If the participant is female and fertile, and if the pregnancy test from the inclusion 
consultation is more than 48 hours old, we will perform another urinary pregnancy test. If the pregnancy 
test is negative, the patient can go through with the project scan. The test result will be documented on the 
PET administration sheet by the scanning personnel and afterwards documented in the eCRF. A peripheral 
venous catheter is placed the cubital fossae for tracer injection. 
 
The participant will then be injected with 1-2MBq/kg of [68Ga]Ga-FAPI-46, with a minimum dose of 100 
MBq and a maximum dose of 246 MBq (30, 39). The content of FAPI-46 in each batch of [68Ga]Ga-FAPI-46 
is limited to 50 µg. The patient will only get a fraction of the full batch of the tracer. This means that the 
dose of [68Ga]Ga-FAPI-46 for each participant never will exceed 50 µg (please refer to the IMPD quality 
page 24). 
 
The patient will then rest for 30-40 min, to let the tracer be distributed within the body. The participant will 
then undergo a PET scan of 10-20 min. The PET scan will cover an area from vertex to mid-thighs as 
standard. However, if the patient has distant metastases on the lower part of the legs/or feet, this will be 
included in the scan. The patient will receive a low dose CT scan, which will be performed prior to the PET 
scan. The radiation dose of the [68Ga]Ga-FAPI-46 PET/CT is approximated to 6 mSv. 
After 12 weeks of ICT, patients will undergo another [68Ga]Ga-FAPI-46 PET/CT, and the same procedure will 
be followed. 
Patients will be observed during both scanning sessions. After 24 hours of the first scan, the patient will be 
contacted by co-investigators or delegated research personnel to check the patients’ condition. Any 
adverse event will be recorded, and the reporting standards stated in section 7 will be followed. 

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4.6 Standard imaging [18F]FDG PET/CT (Comparator) 
Included patients will have undergone a standard [18F]FDG PET/CT for routine clinical purposes before 
entering the trial and starting treatment with ICT. Included patients will also undergo a standard [18F]FDG 
PET/CT for monitoring the disease during treatment. This is standard monitoring procedure for all patients 
with malignant melanoma in treatment with ICT regardless of the inclusion in the trial. These scans will be 
done at Department of Clinical Physiology and Nuclear Medicine, Herlev Hospital or at the Department of 
Clinical Physiology and Nuclear Medicine at Rigshospitalet. 
[18F]FDG is a marketed product. Information regarding handling of the tracer [18F]FDG is described in the 
product resume. The tracer is produced and finalized for administration at the Dept. of Clinical Physiology 
and Nuclear Medicine, Cyclotron section and Radiochemistry, Rigshospitalet, or at Dept. of Clinical 
Physiology and Nuclear Medicine Herlev Hospital, who will comply with directions described in the product 
resume. 
[18F]FDG is a sterile solution for intravenous injection. All incoming raw materials will be registered and 
tested. For each synthesis raw materials used will be documented in a dedicated batch record ensuring full 
traceability. Methods for quality control are validated. [18F]FDG will only be released when all quality 
control tests are within specifications. The Dept. of Clinical Physiology and Nuclear Medicine at Herlev 
Hospital or Rigshospitalet will handle the bookkeeping regarding the use of the compound. 
When the [18F]FDG is administered, the lot number or batch number, the injected dose and the time of 
injection will be documented. This information will be available in the electronical medical record 
(Sundhedsplatformen) of each participant. The information will be documented in the eCRF. As the 
information is available from the personal electronical medical record, the information will be fully 
traceable to the individual participant. At Rigshospitalet, this information will also be documented on a PET 
administration sheet (“PET arbejdsseddel”), which is correlated to each individual participant with their CPR 
number. This sheet will also be saved electronically, which also will secure full traceability. 
 
The procedures of the scans will be done in accordance with local guidelines (please refer to appendix 3). In 
general, the scans will proceed as follows: Before arrival the participant will have to fast for minimum 4 
hours and limit hard physical activity 24 hours before the scan. If the participant suffers from diabetes, 
specific preparation is needed. This is described in detail in local guidelines (please refer to the appendix 3). 
Upon arrival at the Department of Clinical Physiology and Nuclear Medicine at either Herlev Hospital or 
Rigshospitalet, the participant will be placed in a bed in a relaxed prone position. The participant will be 
informed about the outline of the scan, and questioned about relevant conditions (e.g., allergies and 
diabetes) and if the patient has fasted. If the participant is female and fertile, a urinary pregnancy test will 
be performed. If the pregnancy test is negative, the patient can go through with the scan. A peripheral 
venous catheter is placed the cubital fossae for tracer injection. The participant will then be injected with 3- 
4 MBq/kg of [18F]FDG, with a maximum dose of 400 MBq. The participant will then rest for 45-60 min to let 
the tracer be distributed in the body. The patient will then be placed in a PET/CT scanner, and undergo a 
combined PET and CT scan for 15-20 min. 

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4.7 Blood sample 
One 4 ml serum blood sample will be taken prior to each of the [68Ga]Ga-FAPI-46 PET/CT. Blood samples 
will be transferred to the Department of clinical biochemistry Research Section Rigshospitalet immediately 
after the sample has been taken. Trained personnel at the department will handle and store the blood 
samples in a biobank until collected by Nordic bioscience. The blood samples will then be analyzed by 
Nordic bioscience, using an in house competitive ELISA. For more information on blood sample storage and 
analysis please refer to section 8. 
4.8 List of medicinal products: 
4.8.1 Investigational medicinal products 
Product name 
Active ingredient 
Type of medicinal product 
Regulatory 
status 
Reference Safety 
information (RSI) 
[68Ga]Ga-FAPI-46 
[68Ga]Ga-FAPI-46 
A positron emission tomography (PET) 
radioligand for detecting Fibroblast 
Activation Protein (FAP) 
No marketing 
authorization 
Investigators Brochure 
and IMPD 
 
4.8.2 Comparator 
Product name 
Active ingredients 
Purpose in the study 
Regulatory status 
Reference Safety 
information (RSI) 
[18F]FDG 
[18F]FDG 
[18F]FDG is indicated for 
diagnostic use with PET 
Marketing 
authorization 
Product resume, 
see appendix 1. 
 
4.9 Interpretation of project scans 
The baseline and the follow-up [68Ga]Ga-FAPI-46 PET/CT scan will be evaluated using a standardised 
method by a team of experienced specialists in clinical physiology and nuclear medicine. The uptake of 
[68Ga]Ga-FAPI-46 in selected lesions and in normal tissue will also be evaluated. Differences in uptake 
between the baseline project scan and the follow-up project scan will be estimated. Results from the scan 
assessments will be documented in the eCRF. 
If any condition is visible on the project scans that requires urgent medical attention (e.g. pulmonary 
embolism), the participants’ primary physician will be contacted by the co-investigator. In this context, the 
primary physician will most likely be an oncologist from Herlev Hospital. The participants will be informed 
of the condition and treated according to local guidelines by their primary physician. 
4.10 Interpretation of clinical scans 
The clinical standard imaging [18F]FDG PET/CT scans will be used to assess treatment response in the study. 
Treatment response will be evaluated retrospectively using the RECIST criteria (40). The most recently 
updated version of the guideline will be used. The standard imaging will also be evaluated clinically as part 
of the normal treatment monitoring, and patients will get the description of the scan from their primary 
physician, which will be an oncologist from the Department of Oncology at Herlev Hospital. 

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4.11 Endpoint assessment: 
4.11.1 Primary Objectives 
1) Evaluate changes in [68Ga]Ga-FAPI-46 uptake in malignant lesions on [68Ga]Ga-FAPI-46 PET/CT. 
2) Evaluate changes in [68Ga]Ga-FAPI-46-uptake in malignant lesions on [68Ga]Ga-FAPI-46 PET/CT 
during ICT. 
3) Compare the changes in malignant lesions on [68Ga]Ga-FAPI-46 PET/CT with changes on standard 
[18F]FDG PET/CT and clinical response during ICT. 
Specified malignant lesions will be defined and evaluated by a team of specialists on the baseline [68Ga]Ga- 
FAPI PET/CT scan and the uptake of the FAPI tracer in the lesions will be quantified (please refer to section 
4.9). The evaluation of the malignant lesions on [68Ga]Ga-FAPI PET/CT will also be compared with a similar 
lesion evaluation on the [18F]FDG PET/CT (standard imaging). The FAPI-uptake will be reassessed after 12 
weeks of ICT by the same team of specialists. Changes in uptake of malignant lesions after 12 weeks of ICT 
on the [68Ga]Ga-FAPI-46 PET/CT will be compared to changes on the [18F]FDG PET/CT and the clinical 
response. The clinical response will be assessed using the patients’ medical record. 
 
4.11.2 Secondary objectives 
1) Evaluate if changes in [68Ga]Ga-FAPI-46-uptake during ICT in healthy tissue can be used as a 
predictor of potential side effects. 
2) Compare changes in uptake on [68Ga]Ga-FAPI-46 PET/CT in healthy tissue with changes on standard 
[18F]FDG PET/CT. 
Tracer-uptake in healthy tissue and benign lesions on [68Ga]Ga-FAPI-46 PET/CT will be evaluated using the 
same method as described in “Primary Objectives”. A similar evaluation of standard [18F]FDG PET/CT will be 
performed. FAPI-uptake in healthy tissue on [68Ga]Ga-FAPI-46 PET/CT will be compared to the findings on 
[18F]FDG PET/CT. To verify the [68Ga]Ga-FAPI-46 PET/CT assessment (including evaluation of healthy tissue, 
malignant lesions and benign lesions), the assessment will be compared to the findings from a composed 
reference standard. This consist of all available imaging, biopsy results, blood tests, and information on 
hospitalization and changes in patient management up to 6 months after the [68Ga]Ga-FAPI PET/CT. 
 
Changes in FAPI-uptake on the [68Ga]Ga-FAPI PET/CT and FDG-uptake on the standard [18F]FDG PET/CT in 
normal tissue after 3 months of ICT will be evaluated. Changes in FAPI-uptake will also be compared to any 
side effect (IrAE) that the patients may experience during ICT. The presence of IrAE will be determined by 
an expert in oncology, who is blinded from the project scans. The expert will evaluate the patients’ clinical 
records, using all available imaging, biopsy results, information on hospitalization and changes in patient 
management up to 6 months after the baseline [68Ga]Ga-FAPI PET/CT. 
4.11.3 Exploratory objectives: 
1) Correlation between [68Ga]Ga-FAPI-46-uptake on [68Ga]Ga-FAPI-46 PET/CT and levels of FAP-activity 
biomarkers in serum blood samples during ICT. 
2) Correlation between [68Ga]Ga-FAPI-46-uptake on [68Ga]Ga-FAPI-46 PET/CT and levels of other 
biomarkers(e.g. ECM remodeling biomarkers) in serum blood samples. 
3) Correlation between levels of biomarkers in serum blood samples and treatment outcome. 

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Blood samples from the included participants will be analyzed by Nordic Bioscience (please refer to section 
2, Background). Results from this analysis will be correlated to the disease activity evaluated on the 
[68Ga]Ga-FAPI-46 PET/CT. Results from the serum blood sample analysis will also be correlated with 
treatment outcome after 6 months of treatment. Treatment outcome will be defined using the RECIST 
criteria (40). This analysis will be done retrospectively on routine clinical scans (PET/CT). The updated 
guideline and definitions of the RECIST criteria will be used. 
 
5. Statistics: 
5.1 Sample size: 
[68Ga]Ga-FAPI-46 PET/CT has not previously been tested in patients with malignant melanoma in this 
specific setting. The study will be regarded as a pilot study, and we plan to include 20 patients with an 
interim analysis when the first 10 patients have undergone the baseline [68Ga]Ga-FAPI-46 PET/CT (please 
refer to section 6). 
5.2 Statistical analyses: 
All statistical analyses will be conducted using the statistical analysis programs SPSS or R. 
Descriptive statistics will be performed to evaluate patient characteristics and tumor characteristics. For 
description of FAPI-measurements from the scan, the arithmetic mean, standard deviation and median will 
be used. Comparison between [68Ga]Ga-FAPI-46 and [18F]FDG evaluation of malignant lesions (primary 
tumor and metastases) and normal tissue will be performed with a paired non-parametric test or a paired 
student’s t-test. Changes on the [68Ga]Ga-FAPI-46 will be correlated to the result from the response 
assessment using a non-parametric test (e.g. Kruskal Wallis test). A similar method will be used to evaluate 
FAPI-uptake changes in normal tissue and the correlation to IrAE. 
Correlation between FAPI-uptake and results from the blood samples will be compared using statistical 
correlation-tests (e.g. Spearman rank correlation). The correlation between treatment outcome and levels 
of FAP-activity biomarkers/other relevant biomarkers in the blood will be evaluated using a paired 
student’s t-test or paired non-parametric test. The test could also be performed with a Point Bisereal 
correlation test. 
 
Two-tailed p-value of <0.05 will be considered significant. If any substantial changes in the original 
statistical plan are made (e.g. change in sample size), this will be reported as an amendment. In the Clinical 
Trial Regulation, substantial amendments are named substantial modifications, and a substantial 
modification (amendment) will be submitted via Clinical trial information system (CTIS) to the Danish 
Medicines Agency and the Danish Medical Research Ethics Committee. Data from the included patients will 
be used for all the statistical analyses. Data on participants, who have been excluded after having 
undergone one of the two [68Ga]Ga-FAPI-46 PET/CTs, will be used for selected analyses. Data that turns out 
to be incorrect or false will not be used in the final analysis. Data not used will be stored in the eCRF. 

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6. Interim analysis: 
An interim analysis will be performed after 10 baseline [68Ga]Ga-FAPI-46 PET/CT scans to evaluate quality 
and usefulness of the scans. This will be done by the sponsor/PI and a co-investigator. 
A qualitative analysis of the first 10 scans will be performed. This analysis will determine if the scans have 
the quality to be used for interpretation and evaluation of lesions suspicious of malignancy and also if 
quality of the scans allow readings of uptake-values in suspected lesions. If less than 5 of the first 10 
patients demonstrate FAPI-uptake in known tumors the study will not continue. Otherwise, we will 
continue until 20 evaluable patients (undergoing baseline as well as 3 months follow-up scan) has been 
included. In addition, the sponsor/PI will evaluate the safety of the study. If any unexpected serious adverse 
reactions or serious adverse events after the [68Ga]Ga-FAPI-46 PET/CT scan have occurred at that time 
point, the trial will be stopped. We do not expect to end the trial prematurely due to safety, as no serious 
adverse reaction or events have been reported in previous trials. 
 
7. Side effects and Risks 
7.1 Side effects of the investigational medicinal product 
[68Ga]Ga-FAPI-46 tracer: No adverse reaction or events have been reported in the first radiation dosimetry 
and biodistribution studies of [68Ga]Ga-FAPI-46 (30, 41, 42) and in later phase II studies (31, 32). More than 
1000 patients have been scanned with this tracer without any other reporting of side effects. There is, 
however, always a risk of unexpected side effects or allergic reactions as with all other medications. 
7.2 Side effects of the comparator 
[18F]FDG tracer: [18F]FDG is a standard tracer used for PET/CT in diagnostic cancer imaging, including for 
monitoring and diagnosing patients with malignant melanoma. There is a low probability of side effects 
after administration of [18F]FDG. The tracer is contraindicated in patients with hypersensitivity reaction to 
any active substance or excipients in the solution. The sensitivity of the [18F]FDG PET examination can be 
compromised by medicinal products that affect blood glucose levels (e.g. corticosteroids) and insulin levels, 
which should be taken into consideration before the examination (please refer to product resume, 
appendix 1, section 4.5 and 4.8). The [18F]FDG PET/CT scan is a standard evaluation scan, which will be 
conducted as a part of the routine clinical examinations for the included patients, and will be done 
regardless of the inclusion in the trial. 
7.3 Risks during the study 
The participants receive radiation from radioactive component of the tracer [68Ga]Ga-FAPI-46 and from the 
low-dose CT scans. The radiation dose is approximated to 6 mSv for the [68Ga]Ga-FAPI-46 PET/CT with low 
dose CT. Thus, the total radiation burden for both [68Ga]Ga-FAPI-46 PET/CT scans is 12 mSv. This is 
equivalent to 4 times the annual background radiation in Denmark (3mSv). The accumulative radiation dose 
increases the life-time risk of untreatable cancer per scan with 5% * 0.006 Sv = 0.03% compared to the rest 
of the population(43). The participants will undergo two scans during the trial, why the increased lifetime 
risk will be 0.03%*2 = 0.06%. The lifetime risk of dying from untreatable cancer for the general population 
is 25%. Thus, the two additional sets of scans ([68Ga]Ga-FAPI-46 PET/CT) will increase the lifetime risk from 
25% to 25.06%. 

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The radiation burden from the standard [18F]FDG PET/CT is approximately 12-15 mSv. This scan will be done 
regardless of the inclusion of the trial. 
Other risks during PET/CT scans include claustrophobia and fear of needles. During the insertion of the 
needle, there is a minimal risk of infection and hematoma. These risks are also present during the blood 
sample prior to the PET/CT. 
7.4 Safety 
A qualified medical doctor will be present in the department during the [68Ga]Ga-FAPI-46 PET/CT scans and 
at the routine [18F]FDG PET/CT. Emergency equipment is available in accordance with current procedures of 
the department, including cardiopulmonary resuscitation (CPR) and oxygen supply/suction. The staff of the 
department is trained to handle emergencies and the applicable standard procedures will be followed in 
case of anaphylaxis or other allergic reactions. 
In case the participants experience an adverse reaction or show signs of an adverse reaction or allergic 
reaction during the [68Ga]Ga-FAPI-46 PET/CT, the participant will be appointed and, if necessary, treated by 
local staff until the participant no longer has clinical signs of adverse reactions. The patient will be admitted 
at Rigshospitalet through the Trauma Center. 
If the participant experience any side effects during the routine [18F]FDG PET/CT scan, the patient will be 
treated in accordance with local guidelines at the hospital where the participant undergoes the scan. 
7.5 Registration of side effects and events 
Participants will be observed during the [68Ga]Ga-FAPI-46 PET/CT scan for adverse reaction and events, and 
will be contacted one time, 24 hours after they’ve been injected with the tracer [68Ga]Ga-FAPI-46 and 
undergone the first [68Ga]Ga-FAPI-46 PET/CT and questioned on adverse reaction/adverse events. 
The risk of side effects or adverse events when using [68Ga]Ga-FAPI-46 is expected to be low based on 
previous studies. During the first 24 hours after administration, adverse events (AE), serious adverse events 
(SAE) will be reported in the eCRF and assessed as potential adverse reactions (AR). There are no expected 
AR or serious adverse reactions (SAR) to the administration of [68Ga]Ga-FAPI-46. 
The half-life of the radioactive probe [68Ga] (bound to the FAPI compound) is 68 min, and it is estimated 
that a majority of the compound is non-measureable within 3xhalf-life of the compound. Preclinical studies 
have also shown that a majority of the FAPI compound bound is excreted within the first 24 hours (41, 44). 
Therefore, it is believed that potential side effects of the tracer will be evident within the first 24 hours 
after administration. 
 
The following definitions on AE, SAE, AR, SAR and suspected unexpected serious adverse reactions 
(SUSARS) as well as reporting standards are based on the “Detailed guidance on the collection, verification 
and presentation of adverse even/reaction arising from clinical trials on medicinal products for human use”, 
stated by the European Commission. 
An AE is defined as “any untoward medical occurrence in a patient or clinical trial subject administered a 
medicinal product and which does not necessarily have a causal relationship with this treatment”. The PI is 
responsible for carrying out causality assessment of AEs and will update the protocol accordingly. 
An AR is defined as “all untoward and unintended responses to an investigational medicinal product related 

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to any dose administered”. 
An SAE is defined: “any untoward medical occurrence or effect that at any dose results in death, is life- 
threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or 
significant disability or incapacity or is a congenital anomaly or birth defect”. SAEs of investigational 
medicinal product ([68Ga]Ga-FAPI-46) must be reported within 24 hours by the investigators to the 
PI/sponsor. 
SAR is defined as the above-mentioned AR, however with the addition of “serious” which covers the 
following: “… results in death, is life-threatening, requires hospitalization or prolongation of existing 
hospitalization, results in persistent or significant disability or incapacity or is a congenital anomaly or birth 
defect”. SARs are divided into the expected and unexpected SARs, where the unexpected adverse reaction 
is defined as: “an adverse reaction, the nature or severity of which is not consistent with the applicable 
product information (e.g. investigator’s brochure for an unauthorised investigational product or summary 
of product characteristics for an authorised product)”(45). 
As there are no expected serious adverse reactions to the administration of [68Ga]Ga-FAPI-46, all SARs will 
be considered SUSARs . 
SUSARS will be reported by the sponsor immediately to the regulatory authorities via EudraVigilance as 
soon as possible and no longer than 15 days. If the SUSARS result in death or is life threatening, the sponsor 
will report the incident within seven days after being made aware of the case. Within eight days after this 
reporting, the sponsor needs to send all relevant information in a follow-up report. The reporting of 
SUSARS will be done in accordance with the current reporting practice. Any report must be accompanied by 
comments on any consequences for the trial. 
Throughout the duration of the trial, the sponsor will annually report a list of occurred suspected serious 
adverse reactions, and a report on the subject’s safety via CTIS. All adverse reactions and events will be 
collected in a final report and send to CTIS within 1 year after the end of the trial. 
The reference safety information (RSI) that will be used to asses AR and AE, will be the IMPD and 
Investigator’s Brochure for the tracer [68Ga]Ga-FAPI-46. 
The RSI of the comparator [18F]FDG is the product resume (appendix 1). Side effects related to the 
comparator product [18F]FDG is exempted from reporting of AE, AR, SAE and SAR but not SUSARs due to the 
low risk profile (risk adapted adverse event management, please refer to appendix 2). [18F]FDG is an 
authorised medicinal product, with low risk of adverse reactions (please refer to the product resume, 
appendix 1, section 4.8). [18F]FDG is used for an approved indication in which the intervention is normal 
clinical practice. As such, the risk profile is believed to be low. However, investigators are allowed to report 
any SAEs immediately at their own discretion. 
Registration of the events not exempted from reporting will be assessed within the first 24 hours after 
administration of [18F]FDG. This will be done by evaluating the patients’ electronic medical record. 
All investigator reported events will be registered in the annual safety report. The annual safety report will 
describe the rules of registration and reporting of adverse events as given in this protocol. 

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8. Collection of biological material 
One 4 ml serum blood samples will be taken before each scan. Thus, two serum blood samples will be 
taken during the trial. In total we will collect 8 ml of blood. 
The blood samples will be transferred to the Department of Clinical Biochemistry Research Section 
Rigshospitalet as soon as possible after the sample has been taken. Trained personnel at this department 
will carry out the initial preparations of blood samples. Blood samples will clot for a minimum of 30 minutes 
at room temperature. Then, the sample will be centrifuge at 2000g for 10 minutes at +4°C or room 
temperature and no longer than 1 hour after sampling. The samples will then be transferred to 2 x 2ml 
cryo-tubes. The sample will be stored for 30 min in the storage box at -20°C or below for up to two weeks. 
For long term storage, the samples will be moved to a -80°C freezer. The blood samples will be 
pseudonymized with a project number. 
The sample biobank will be stored at the Department of Clinical Biochemistry Research Section 
Rigshospitalet until collected by Nordic Bioscience. A list of the collected and stored blood samples will be 
available at the Department of Clinical Biochemistry Research Section Rigshospitalet. When all the blood 
samples have been collected (total of 40 samples), the samples will be transferred to Nordic bioscience. 
A list of the transferred blood samples will be available in the TMF. 
The samples will be analyzed by Nordic bioscience, using an in house competitive ELISA. Additionally, 
Nordic Bioscience will measure other tumor fibrosis biomarkers e.g., PRO-C3 (type III collagen formation). 
This to get the full picture of the tumor fibrotic responses associated with FAP-expression in cancer 
patients. A mean of 50 uL sample would be used for the assessment of each of the protein fingerprint 
markers including quality control assessments. Serum samples are run in duplicates. Around 50 uL will be 
used for the assessment of a single protein fingerprint markers including re-running samples with a CV% 
above the limit (20%). 
After the analysis, all biological material will be destroyed. 
The samples will primarily be stored at the Department of clinical biochemistry Research Section 
Rigshospitalet until all patients have been included and completed the study (maximum 2 years). The 
analysis of blood samples will be conducted at Nordic Bioscience. Here the material will be stored for up to 
1 month. The unused biological material will be destroyed after analysis. Nordic Bioscience will retain a 
copy of the results from the measurements of the blood samples. The data will be pseudonymized. Nordic 
Bioscience will however not have access to the pseudonymization key. All results from the blood samples 
will be destroyed 10 years after the first date of measurement. The results can be used for scientific 
publications in collaboration with Sponsor/PI and after publication, the published data can be used for 
other purposes (e.g., patent application). A contract between Sponsor/PI of the study and Nordic 
Bioscience regarding these tasks will be made. 
 
9. Data Management: 
9.1 Respect for participants’ physical and mental integrity and right to privacy: 
The Danish health law, the Danish Data Protection Act and General Data Protection Regulation (GDPR) 
protect all participants in this trial (46). The trial will be reported to The Knowledge Centre of Data 
Protection Compliance at the Capital Region. 

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According to the Data Protection Act and Law Enforcement Directive, all data will be securely kept at the 
Dept. of Clinical Physiology and Nuclear Medicine, Rigshospitalet. A list revealing the identity of each 
participant will be kept locked-in at the Dept. of Clinical Physiology and Nuclear Medicine, Rigshospitalet on 
a local computer drive. These folders have restricted access, which only can be granted from the Centre of 
IT and Medical Technology (CIMT, Capital region), and the owner of the locked folders, which is an 
investigator. The eCRF will be stored in the database REDcap. Access to data in REDcap will be restricted to 
specified research workers. To gain access to REDcap, research workers need to be granted access by CIMT, 
Capital Region. A 2-step verification log-in is required to access REDcap. The owner of the eCRF (also called 
the project owner) will have the responsibility to grant access to the data set. The project owner of the 
eCRF will be an investigator. 
 
Pseudonymized data will be stored in 25 years after trial finalization in accordance with the current 
legislation. At any given time the Good Clinical Practice (GCP)-unit, and representatives from the Danish 
Medical Research Ethics Committee, and the Danish Medicines Agency will be able to gain access to the 
source data in the patient medical record for monitoring and inspection. Research workers involved in the 
trial will also have access to the medical records for included participants. All data will be handled 
confidentially. 
In the case of any data security breaches, the procedures and guidelines from the Capital Region and 
Rigshospitalet will be followed to mitigate possible adverse effects. 
The participants must allow that pseudonymous scan-pictures can be used for publicly available 
publications, teaching purposes, and extern evaluation. The scan pictures will not include information that 
will identify the patients (such as dates, social security number or birthday). The use of scans will comply 
with GDPR, the Danish Data Protection Act and the Clinical Trial Regulation, article 28, section 1 (d-e). 
9.2 Information from and interpretation of the [68Ga]Ga-FAPI-46 PET/CT scans: 
The batch number, injected dose, time of injection, and patients’ height and weight will be documented on 
the PET administration sheet during the [68Ga]Ga-FAPI-46 PET/CT scan. This is a routine procedure for the 
scanning personnel at the Dept. of Clinical Physiology and Nuclear Medicine. The PET administration sheet 
will be regarded as source data and the information will be recorded on eCRF. The analysis of the [68Ga]Ga- 
FAPI-46 PET/CT scan will be performed by specialists on routine computer programs and afterwards 
documented in the eCRF by a co-investigator. 
9.3 Analysis of blood samples 
The results from the FAP-activity blood sample will be recorded in a secure database according to standard 
operating procedure at Nordic Bioscience. This dataset will be regarded as source-data. The results from 
the analysis will be send to the PI/Sponsor or co-investigator using a secure mail-system and recorded in 
the eCRF. 
9.4 Information from the clinical record: 
The following information will be registered in the eCRF for each trial participant and regarded as source 
information from the participant’s electronical medical record and utility programs connected to the 
electronical medical record: 

Protocol Version 4, June 2025 
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Variable 
Reasons for registration 
Age, gender, BMI. 
For publication, background variables are required to verify that 
the participants are representative of the investigated group. 
Inclusion and exclusion criteria. 
To be able to include/exclude participants of the trial. This data 
will be acquired before the patient has given written and 
informed consent. This include: disease history, medicine, 
allergies, tumor biopsy material and treatment decision. 
Cancer diagnosis, classified by the 
TNM classification system, 
anatomical location, histological 
type of tumor, and analysis of 
receptor-expression. Previous and 
current medication for cancer 
diseases. 
For publication, background variables are required to verify that 
the participants are representative of the investigated group. 
Other diseases and medication. 
Other known disease/malignancies may affect the interpretation 
of the [68Ga]Ga-FAPI-46 PET scan. 
Standard imaging ([18F]FDG PET/CT). 
Lot number/batch number, administered dose, time and date of 
injection, images as well as the description of the scan from the 
routine diagnostic examinations. This will be used for registration 
of the comparator product and to assess treatment response 
during the follow up period. 
Follow-up data 6 months after the 
[68Ga]Ga-FAPI-46 PET : scans, clinical 
records, histology, and pathology 
samples, blood samples. 
Follow up data are necessary to be able to verify tracer-uptake 
on [68Ga]Ga-FAPI-46 PET in normal tissue and malignant lesions 
and are necessary to be able to correlate tracer uptake in normal 
tissue and malignant lesions to potential adverse reaction (IrAE). 
This will also be done to be able to correlate blood sample results 
with treatment outcome. 
 
The eCRF will be stored in REDCap. 
9.5 Quality control and monitoring: 
The GCP-unit of Copenhagen University Hospital will monitor the trial. Monitoring visits will be conducted 
before, during and at the end of the trial. The visits will ensure that the trial is conducted according to the 
protocol and to the GCP regulations. 
 
10. 
Science and ethics 
The trial will be conducted in accordance with the protocol and the laws and regulations of the Danish state 
as well as applicable regulations from the European Commission. In addition, the trial will be conducted in 
accordance with the International Conference on Harmonisation-Good Clinical Practice (ICH-GCP) 
regulations and the common principals of good clinical practice. 
All eligible participants will receive the standard treatment and standard surveillance of their cancer, no 
matter their participation status. The patients will not be informed of the results from the [68Ga]Ga-FAPI-46 
PET/CT , and the results will not affect their individual treatment or surveillance. This is clearly stated in the 

Protocol Version 4, June 2025 
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participant information. Participants, who wish to gain access to the results from the trial, are allowed to 
do so, when the trial is finished. 
The potential risks of the trial are believed to be low. The increased radiation burden is approximately 4 
times of the annual background radiation in Denmark (3mSv) for both scans. The life-time risk of 
untreatable cancer will increase with 0.06% compared to the rest of the population. Based on previous 
experience with the tracer [68Ga]Ga-FAPI-46 the risk of experiencing side effects is low. 
 
The radiation burden of the standard [18F]FDG PET/CT is 12-15 mSv. The [18F]FDG PET/CT is a standard 
evaluation scan, which is performed during treatment with ICT. As such, the scan will be done regardless of 
the inclusion in the trial. The risk of any adverse reactions to the [18F]FDG is believed to be low (please refer 
to the product resume, section 4.8, appendix 1). 
The [68Ga]Ga-FAPI-46 PET/CT is believed to improve response evaluation of patients with malignant 
melanoma treated with ICT, early detection of side effects to ICT, and patient comfort during PET/CT scans. 
We believe that these potential benefits outweigh the potential risk of the trial. 
10.1 Guidelines for participants’ information and written consent 
The recruitment arrangements are described in the document “Recruitment arrangements” in part II of the 
application dossier. 
10.2 Written consent 
All participants must sign a written consent form to be able to participate in the trial. 
The participants must allow that pseudonymous scan-pictures can be used for publicly available 
publications, teaching purposes, and extern evaluation. The patients most also allow for the analysis of 
blood samples and storage in a biobank (please refer to section 8). This will be clearly stated in the written 
consent form. 
The participant must also allow all researchers involved in the trial (sponsor, PI, co-investigators, delegated 
research personnel) to obtain information from his/her medical record necessary to conduct the research. 
Participants must also allow representatives from the Danish Medical Agency, the GCP-unit of Copenhagen 
University and the Danish Medical Research Ethics Committee to examine his/her medical record for 
quality assessment, quality control and security of the trial. All information will be handled confidentially. 
The investigators are responsible for obtaining the written and oral consent from the participant before the 
participant undergo any trial-related procedures. All signed consent forms will be transferred and stored at 
the Department of Clinical Physiology and Nuclear Medicine, Rigshospitalet in the TMF. 
 
11. 
Publication of results 
The trial will be registered at clinicaltrials.gov as well as CTIS. During the publications process, the 
Vancouver Recommendations will be followed. The results will be published on CTIS and in international 
English-speaking peer reviewed journals as open access. All results will be published including positive, 
negative, and inconclusive findings. As stated in the participant information, pseudonymized scan-pictures 
can be used in both papers and presentations. The order of authors on the primary publications will be a 

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co-investigator as first author, and last author will be either the sponsor or on of the advisors. Both 
preliminary and final results will potentially be presented at relevant international conferences. 
 
12. 
Insurance 
The trial will be conducted at Rigshospitalet and the sponsor (BMF) and PI will be employed by 
Rigshospitalet and the Capital Region. Thus, participants in the study are legally regarded as patients, and 
will be covered by the normal insurance of patients hospitalized at Rigshospitalet as well as the normal 
insurance for patients stated by the Danish Law (Den offentlige patienterstatningsordning). 
 
13. 
Timeframe of the trial 
The inclusion of patients is expected to start in the spring of 2025, and inclusion period is expected to last 
for 1 year. All patients have a follow-up period of 6 months. The trial will end 6 months after the last 
participant has completed their second [68Ga]Ga-FAPI-46 PET/CT. Data will be stored for 25 years after the 
collected data has been processed. 

Protocol Version 4, June 2025 
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14. 
Protocol Synopsis 
 
[68Ga]Ga-FAPI-46 PET/CT for Better and Faster imaging in cancer 
Protocol: [68Ga]Ga-FAPI PET/CT for response evaluation during immune checkpoint inhibitor therapy in 
malignant melanoma patients in immune checkpoint inhibitor therapy 
EU trial number: 
2023-509549-11-00 
Rationale of the study: 
Malignant melanoma is a highly aggressive cancer and is treatment resistant especially in advanced stages. 
The introduction of immunotherapy and especially immune checkpoint inhibitor therapy (ICT) have 
improved survival rates for malignant melanoma patients with advanced stages. Current standard imaging 
for treatment monitoring with [18F]FDG PET/CT lacks specificity in discriminating between side effects from 
ICT (immune related adverse events, IrAEs) and progression of cancer. Clear discrimination is a necessity for 
clinicians to be able to quickly optimize and change treatment strategy. Fibroblast activating protein 
inhibitor (FAPI) is a specific enzyme inhibitor that binds to fibroblast activating protein (FAP) expressing 
cells. FAP is found on cancer associated fibroblasts (CAFs) that exist in the tumor supporting tissues in 
epithelial cancers. FAP is upregulated in 90% of epithelial neoplasms and malignant melanoma. FAPI 
radiolabeled with gallium-68 ([68Ga]Ga-FAPI, synonym [68Ga]FAPI) has proven potential as a 
radiopharmaceutical agent in PET imaging for detection of malignant primary tumors as well as distant 
metastases in different cancer types. Case reports have demonstrated promising results in using [68Ga]FAPI 
PET to visualize malignant melanoma cancer lesions. In addition, the potential use of [68Ga]FAPI in 
diagnosing IrAEs have also been demonstrated in case reports and one feasibility study. 
Therefore, we propose a clinical phase II clinical trial to investigate the potential use of the tracer [68Ga]FAPI 
for PET/CT-imaging in patients with advanced stage malignant melanoma referred for ICT. 
The activity of the protein FAP may be measured in liquid biopsies/blood samples from cancer patients. 
Nordic bioscience has developed a method to measure specific molecules in serum blood samples, which 
reflects FAP activity, from now on called FAP activity biomarkers. Therefore, we want to explore the 
correlation between FAP activity biomarkers with the FAPI-uptake on [68Ga]FAPI PET imaging of patients 
with malignant melanoma. These biomarkers could be a potential screening tool for selecting the right 
patients to receive a PET/CT scan and to provide a way to monitor the patients between PET/CT scans. 
Study hypothesis: 
- 
[68Ga]Ga-FAPI PET/CT can improve response evaluation in patients suffering from advanced stage 
malignant melanoma treated with ICT and potentially serve as a biomarker. 
Objectives and endpoints: 
The aim of the study is to evaluate [68Ga]FAPI PET/CT as a non-invasive diagnostic tool for response 
evaluation during ICT in patients with advanced stage malignant melanoma. 

Protocol Version 4, June 2025 
29 
 
The primary endpoint will be to evaluate changes in FAPI-uptake in both primary tumor and metastases on 
[68Ga]FAPI PET/CT during ICT. These findings will be compared to changes in [18F]FDG-uptake on standard 
imaging. The secondary endpoints will be to evaluate changes in [68Ga]FAPI-uptake in healthy tissue on 
[68Ga]FAPI PET/CT during ICT. This assessment will also be compared to findings on standard imaging as 
well. Changes in FAPI-uptake will also be compared to any side effect (IrAE) that the patients may 
experience during ICT. The presence of IrAE will be determined by an expert in oncology, who is blinded 
from the project scans. The [68Ga]FAPI PET/CT assessment (including evaluation of healthy tissue and 
malignant lesions) will be compared to the findings from a composed reference standard. This will consist 
of all available imaging, biopsy results, blood tests, and information on hospitalization and changes in 
patient management up to 6 months after the [68Ga]FAPI PET/CT. 
The exploratory endpoint will evaluate the correlation between [68Ga]Ga-FAPI-uptake and the level of FAP- 
activity biomarkers in blood samples from included patients. In addition, we will correlate results from the 
biomarker analysis with treatment outcome of immunotherapy within 6 months of treatment using the 
Response Evaluation Criteria in Solid Tumors (RECIST) criteria. 
Trial Design and trial population 
The study is a phase II nonrandomized clinical trial evaluating [68Ga]FAPI PET/CT for response evaluation 
during ICT in patients with advanced stage malignant melanoma with visible target lesions on [18F]FDG 
PET/CT. The study will be regarded as a pilot study and include 20 patients. 
The included participants will undergo two scans in addition to their standard imaging (diagnostic [18F]FDG 
PET/CT). At baseline the patients will undergo a [68Ga]FAPI PET/CT. This will be performed before initiation 
of ICT. A blood sample will be collected prior to injection of the tracer. After 12 weeks of treatment, the 
participant will undergo another [68Ga]FAPI PET/CT and a second blood sample in addition to their standard 
imaging (diagnostic [18F]FDG PET/CT). During the [68Ga]FAPI PET/CT, participants will be observed for 
adverse events and reactions. In addition, the participants will be contacted 24 hours after the first scan to 
evaluate potential adverse events or reactions. Thus, participants will be included for two [68Ga]FAPI 
PET/CT and two blood samples. The patients will also be followed for period of 6 months after the last 
scanning session using the patients’ medical record. 
Intervention 
Participants will undergo two [68Ga]FAPI PET/CT scans at the department of Clinical Physiology and Nuclear 
Medicine, Copenhagen University Hospital, Rigshospitalet. The first scan will be performed prior to 
initiation of ICT and the second scan will be performed after 12 weeks of ICT-treatment. 
 
Upon arrival, the participant will be placed in a bed in a relaxed prone position. If the participant is female 
and fertile, and if the pregnancy test from the inclusion consultation is more than 48 hours old, we will 
perform another urinary pregnancy test. If the pregnancy test is negative, the patient can go through with 
the project scan. 
 
The participant will then be injected with 1-2MBq/kg of [68Ga]FAPI, with a minimum dose of 100 MBq and a 
maximum dose of 246 MBq. The patient will then rest for 30-40 min and then undergo a PET scan for 10-20 
min. The PET scan will cover an area from vertex to mid-thighs. The patient will also undergo a low dose CT 
scan, which will be performed prior to the PET scan. After 12 weeks of ICT, patients will undergo the second 

Protocol Version 4, June 2025 
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[68Ga]FAPI PET/CT and the same procedure will be followed. 
Prior to injection of the tracers in each scan session, a serum blood sample will be taken. 
 
Patients will be observed during the scan session for any adverse events. After 24 hours, after the first 
[68Ga]FAPI PET/CT , the patient will be contacted by co-investigators or delegated research personnel, who 
will check the patients’ condition. 
Safety and risks 
No adverse reaction or events have been reported after injection with [68Ga]FAPI in previous studies. More 
than 1000 patients have been scanned with this tracer without any other reporting of side effects. More 
information on the tracer [68Ga]FAPI is found in the Investigational Medicinal Product Dossier (IMPD) and in 
the Investigator’s Brochure (IB) attached in the application. 
The potential risks of the trial are believed to be low. The increased radiation burden is 6 mSv for each of 
the [68Ga]FAPI PET with low dose CT. This will increase life-time risk of untreatable cancer with 0.06% 
compared to the rest of the population. 
The radiation burden of the standard [18F]FDG PET/CT is 12-15 mSv. The [18F]FDG PET/CT is a standard 
evaluation scan, which is performed during treatment with ICT. As such, the scan will be done regardless of 
the inclusion in the trial. The risk of any adverse reactions to the [18F]FDG is believed to be low (please refer 
to the product resume, appendix 1). 
Ethics and data protection 
The trial will be conducted in accordance the Danish and European laws and regulations on clinical trials, as 
well as ICH-GCP regulations and the common principals of good clinical practice. The Danish health law, the 
Danish Data Protection Act, and General Data Protection Regulation (GDPR) protect all participants in this 
trial (40). The trial will be reported to The Knowledge Centre of Data Protection Compliance at the Capital 
Region. All eligible participants will receive the standard treatment and follow up care of their cancer, no 
matter their participation status. 
The [68Ga]FAPI PET/CT is believed to improve response evaluation of patients with malignant melanoma 
treated with ICT. We believe that these potential benefits outweigh the potential risk of the trial. 
 
15. 
References 
 
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Maio M, Grob JJ, Aamdal S, Bondarenko I, Robert C, Thomas L, et al. Five-year survival rates 
for treatment-naive patients with advanced melanoma who received ipilimumab plus dacarbazine in a 
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Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, et al. Pembrolizumab versus 
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Herrscher H, Robert C. Immune checkpoint inhibitors in melanoma in the metastatic, 
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Guldbrandsen KF, Hendel HW, Langer SW, Fischer BM. Nuclear Molecular Imaging Strategies 
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Boellaard R, Delgado-Bolton R, Oyen WJ, Giammarile F, Tatsch K, Eschner W, et al. FDG 
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Kostakoglu L, Agress H, Jr., Goldsmith SJ. Clinical role of FDG PET in evaluation of cancer 
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Fuster D, Chiang S, Johnson G, Schuchter LM, Zhuang H, Alavi A. Is 18F-FDG PET more 
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Kapoor V, McCook BM, Torok FS. An introduction to PET-CT imaging. Radiographics. 
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Zhou L, Yang K, Andl T, Wickett RR, Zhang Y. Perspective of Targeting Cancer-Associated 
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Sollini M, Kirienko M, Gelardi F, Fiz F, Gozzi N, Chiti A. State-of-the-art of FAPI-PET imaging: a 
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Giesel FL, Kratochwil C, Schlittenhardt J, Dendl K, Eiber M, Staudinger F, et al. Head-to-head 
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cancer patients. Eur J Nucl Med Mol Imaging. 2021;48(13):4377-85. 
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Kratochwil C, Flechsig P, Lindner T, Abderrahim L, Altmann A, Mier W, et al. (68)Ga-FAPI 
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Mokoala K, Emil N, Lawal I, Antke C, Giesel FL, Sathekge M. [68 Ga]Ga-FAPI versus [18F]F- 
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Rong X, Lv J, Liu Y, Wang Z, Zeng D, Li Y, et al. PET/CT Imaging of Activated Cancer-Associated 
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Li K, Liu W, Yu H, Chen J, Tang W, Wang J, et al. 68Ga-FAPI PET imaging monitors response to 
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26. 
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Med Mol Imaging. 2021;48(11):3736-7. 
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Luo Y, Pan Q, Yang H, Li F, Zhang F. Inflammatory Arthritis Induced by Anti-Programmed 
Death-1 Shown in 68Ga-FAPI PET/CT in a Patient With Esophageal Carcinoma. Clin Nucl Med. 
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16. Appendix 

Fluor-18-FDG, radioaktiv injektionsvæske 
Page 1 of 12 
 
 
20 March 2024 
 
 
SUMMARY OF PRODUCT CHARACTERISTICS 
 
for 
Fluor-18-FDG, solution for injection 
 
 
1. 
NAME OF THE MEDICINAL PRODUCT 
Fluor-18-FDG, solution for injection. 
 
2. 
QUALITATIVE AND QUANTITATIVE COMPOSITION 
1 ml contains 14.0 MBq/ml to 7,24 GBq/ml of Fludeoxyglucose 18F) at the date and time 
of calibration. The activity pr. vial ranges from 400 MBq to 210 GBq at the date and time 
of calibration. 
Fluorine (18F) decays to stable oxygen (18O) with a half-life of 110 minutes by emitting a 
positronic radiation of maximum energy of 634 keV, followed by photonic annihilation 
radiations of 511 keV. 
Excipients with known effetcs:  
Sodium 
Ethanol 
 
For the full list of excipients, see section 6.1. 
 
3. 
PHARMACEUTICAL FORM 
Solution for injection. 
Clear, colourless or slightly yellow solution. 
 
 
4. 
CLINICAL PARTICULARS 
4.1 
Therapeutic indications 
This medicinal product is for diagnostic use only. 
 
Fludeoxyglucose (18F) is indicated for use with positron emission tomography (PET) in 
adults and paediatric population. 
 
Oncology: 
In patients undergoing oncologic diagnostic procedures describing function or diseases, 
where enhanced glucose influx of specific organs or tissues is the diagnostic target. The 
following indications are sufficiently documented (see also section 4.4). 
 
Diagnosis: 
- Characterisation of solitary pulmonary nodule. 
 
 

Fluor-18-FDG, radioaktiv injektionsvæske 
Page 2 of 12 
 
- Detection of cancer of unknown origin revealed for example by cervical adenopathy, 
liver or bones metastases. 
- Characterisation of a pancreatic, hepatic or pelvic mass. 
 
Staging: 
- Head and neck cancers including assistance in guiding biopsy. 
- Primary lung cancer. 
- Locally advanced breast cancer. 
- Oesophageal cancer. 
- Carcinoma of the pancreas. 
- Colorectal cancer particularly in restaging recurrences. 
- Malignant lymphoma. 
- Cervix cancer. 
- Ovarian cancer. 
- Malignant melanoma, Breslow >1.5 mm or lymph node metastasis at first diagnosis. 
 
Monitoring of therapeutic response: 
- Malignant lymphoma. 
- Head and neck cancers. 
 
Detection in case of reasonable suspicion of recurrences: 
- Glioma with high grade of malignancy (III or IV). 
- Head and neck cancers. 
- Thyroid cancer (non-medullary): patients with increased thyroglobulin serum levels 
and negative radioactive iodine whole body scintigraphy. 
- Primary lung cancer. 
- Breast cancer. 
- Carcinoma of the pancreas. 
- Colorectal cancer. 
- Cervix cancer. 
- Ovarian cancer. 
- Malignant lymphoma. 
- Malignant melanoma. 
 
Cardiology: 
In the cardiologic indication, the diagnostic target is viable myocardial tissue that takes-up 
glucose but is hypo-perfused, as it must be assessed beforehand using appropriate blood- 
flow imaging techniques. 
- Evaluation of myocardial viability in patients with severe impaired left ventricular 
function who are candidates for revascularisation when conventional imaging mo- 
dalities are not contributive. 
 
Neurology: 
In the neurologic indication the interictal glucose hypometabolism is the diagnostic target. 
- Localisation of epileptogenic foci in the presurgical evaluation of partial temporal epi- 
lepsy. 
 
Infectious or inflammatory diseases:  
In infectious or inflammatory diseases, the diagnostic target is tissue or structures with an 
abnormal content of activated white blood cells. 

Fluor-18-FDG, radioaktiv injektionsvæske 
Page 3 of 12 
 
In infectious or inflammatory diseases, the following indications are sufficiently docu- 
mented: 
 
Localisation of abnormal foci guiding the aetiologic diagnosis in case of fever of unknown  
origin  
 
Diagnosis of infection in case of: 
- Suspected chronic infection of bone and/or adjacent structures: osteomyelitis, spon- 
dilitis, diskitis or osteitis including when metallic implants are present. 
- Diabetic patient with a foot suspicious of Charcot’s neuroarthropathy, osteomyelitis 
and/ or soft tissue infection. 
- Painful hip prosthesis. 
- Vascular prosthesis. 
- Fever in an AIDS patient. 
- Detection of septic metastatic foci in case of bacteremia or endocarditis (see also sec- 
tion 4.4). 
 
Detection of the extension of inflammation in case of:  
- Sarcoidosis. 
- Inflammatory bowel disease. 
- Vasculitis involving the great vessels. 
Therapy follow-up:  
Unresectable alveolar echinococcosis, in search for active localisations of the parasite dur- 
ing medical treatment and after treatment discontinuation 
 
4.2 
Posology and method of administration 
Posology 
 
Adults and elderly population 
The recommended activity for an adult weighing 70 kg is 100 to 400 MBq (This activity 
has to be adapted according to the body weight of the patient, the type of camera used and 
acquisition mode), administered by direct intravenous injection. 
 
Renal and hepatic impairment 
Careful consideration of the activity to be administered is required since an increased 
radiation exposure is possible in these patients. 
 
Extensive dose range and adjustment studies with this medicinal product in normal and 
special populations have not been performed. 
 
The pharmacokinetics of fludeoxyglucose (18F) in renally impaired patients has not been 
characterised. 
 
Paediatric population 
The use in children and adolescents has to be considered carefully, based upon clinical 
needs and assessing the risk/benefit ratio in this patient group. The activities to be 
administered to children and adolescents may be calculated according to the 
recommendations of the European Association of Nuclear Medicine (EANM) paediatric 
dosage card; the activity administered to children and adolescents may be calculated by 

Fluor-18-FDG, radioaktiv injektionsvæske 
Page 4 of 12 
 
multiplying a baseline activity (for calculation purposes) by the weight-dependent 
multiples given in the table below. 
A [MBq]Aministered =Baseline Activity X Multiple 
The baseline activity for 2D imaging is 25.9 MBq and for 3D imaging 14.0 MBq 
(recommended in children). 
 
Weight 
[kg] 
Multiple 
Weight 
[kg] 
Multiple 
Weight 
[gg] 
Multiple 
3 
1 
22 
5.29 
42 
9.14 
4 
1.14 
24 
5.71 
44 
9.57 
6 
1.71 
26 
6.14 
46 
10.00 
8 
2.14 
28 
6.43 
48 
10.29 
10 
2.71 
30 
6.86 
50 
10.71 
12 
3.14 
32 
7.29 
52-54 
11.29 
14 
3.57 
34 
7.72 
56-58 
12.00 
16 
4.00 
36 
8.00 
60-62 
12.71 
18 
4.43 
38 
8.43 
64-66 
13.43 
20 
4.86 
40 
8.86 
68 
14.00 
 
Method of administration: 
For intravenous use. 
 
For multidose dose use. 
The activity of fludeoxyglucose (18F) has to be measured with an activimeter immediately 
prior to injection. The injection of fludeoxyglucose (18F) must be intravenous in order to 
avoid irradiation as a result of local extravasation, as well as imaging artefacts 
For instructions on dilution of the medicinal product before administration, see section 12. 
For patient preparation, see section 4.4 
Image aquisition 
The emission scans are usually started 45 to 60 minutes after the injection of 
fludeoxyglucose (18F). Provided a sufficient activity remains for adequate counting 
statistics, fludeoxyglucose (18F)-PET can also be performed up to two or three hours after 
administration, thus reducing background activity. 
 
If required, repeated fludeoxyglucose (18F) can be reiterated within a short period of time. 
 
4.3 
Contraindications 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
4.4 
Special warnings and precautions for use 
Potential for hypersensitivity or anaphylactic reactions 
If hypersensitivity or anaphylactic reactions occur, the administration of the medicinal 
product must be discontinued immediately and intravenous treatment initiated if necessary. 

Fluor-18-FDG, radioaktiv injektionsvæske 
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To enable immediate action in emergencies, the necessary medicinal products and 
equipment such as endotracheal tube and ventilator must be immediately available. 
 
Individual benefit/risk justification 
For each patient, the radiation exposure must be justifiable by the likely benefit. The 
activity administered should in every case be as low as reasonably achievable to obtain the 
required diagnostic information. 
 
Renal and hepatic impairment 
Due to the major renal excretion of fludeoxyglucose (18F) in patients with reduced kidney 
function, careful consideration of the benefit risk ratio in these patients is required since an 
increased radiation exposure is possible. Activity should be adjusted if necessary. 
 
Paediatric population 
For information on the use in paediatric population, see sections 4.2 or 5.1. 
Careful consideration of the indication is required since the effective dose per MBq is 
higher than in adults (see section 11). 
 
Patient preparation 
Fluor-18-FDG should be given to sufficiently hydrated patients fasting for a minimum of 4 
hours, in order to obtain a maximum target activity, since glucose uptake in the cells is 
limited (“saturation kinetics”). The amount of liquid should not be limited (beverages 
containing glucose must be avoided). 
 
In order to obtain images of best quality and to reduce the radiation exposure of the 
bladder, patients should be encouraged to drink sufficient amounts and to empty their 
bladder prior to and after the PET examination. 
 
Oncology and neurology and infectious diseases 
In order to avoid hyperfixation of the tracer in muscle, it is advisable for patients to avoid 
all strenuous physical activity prior to the examination and to remain at rest between the 
injection and examination and during acquisition of images (patients should be 
comfortably lying down without reading or speaking). The cerebral glucose metabolism 
depends on the brain activity. Thus neurological examinations should be performed after a 
relaxation period in a darkened room and with low background noise. 
 
A blood glucose test should be performed prior to administration since hyperglycaemia 
may result in a reduced sensitivity of Fluor-18-FDG, especially when glycaemia is greater 
than 8 mmol/l. Similarly, PET with fludeoxyglucose (18F) should be avoided in subjects 
presenting uncontrolled diabetes. 
 
Cardiology 
Since glucose uptake in the myocardium is insulin-dependent, for a myocardial 
examination a glucose loading of 50 g approximately 1 hour prior to the administration of 
Fluor-18-FDG is recommended. Alternatively, especially for patients with diabetes 
mellitus, the blood sugar level can be adjusted by a combined infusion of insulin and 
glucose (Insulin-Glucose-Clamp) if needed. 

Fluor-18-FDG, radioaktiv injektionsvæske 
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Interpretation of the PET with fludeoxyglucose (18F) images 
In the exploration of inflammatory bowel diseases, diagnostic performance of 
fludeoxyglucose (18F) has not been directly compared with that of scintigraphy using 
labelled white blood cells which may be indicated prior to fludeoxyglucose (18F) PET or 
after fludeoxyglucose (18F) PET when inconclusive. 
Infectious and/or inflammatory diseases as well as regenerative processes after surgery can 
result in a significant uptake of fludeoxyglucose (18F) and therefore lead to false positive 
results, when search for infectious or inflammatory lesions is not the aim of the 
18 
18 
fludeoxyglucose ( F) PET In cases where fludeoxyglucose ( F) accumulation can be 
caused by either cancer, infection or inflammation, additional diagnostic techniques for the 
determination of the causative pathologic alteration may be required to supplement the 
18 
information obtained by PET with fludeoxyglucose ( F). In some settings e.g. staging of 
myeloma, both malignant and infectious foci are searched for and may be distinguished 
with a good accuracy on topographic criteria e.g. uptake at extramedullary sites and/or 
bone and joint lesions would be atypical for multiple myeloma lesions and identified cases 
associated with infection. There are currently no other criteria to distinguish infection and 
18 
inflammation by means of fludeoxyglucose ( F) imaging. 
 
Because of the high physiologic uptake of fludeoxyglucose ( 
18 
18 
F) within brain, heart and 
kidneys, PET/CT with fludeoxyglucose ( F) has not been evaluated for the detection of 
septic metastatic foci in these organs when the patient has been referred due to bacteraemia 
or endocarditis 
False positive or false negative PET with fludeoxyglucose (18F) results cannot be excluded 
after radiotherapy within the first 2-4 months. If the clinical indication is demanding an 
earlier diagnosis by PET with fludeoxyglucose (18F), the reason for earlier PET with 
fludeoxyglucose (18F) examination must be reasonably documented. 
 
A delay of at least 4-6 weeks after the last administration of chemotherapy is optimal, in 
particular to avoid false negative results. If the clinical indication is demanding an earlier 
diagnosis by PET with fludeoxyglucose (18F), the reason for earlier PET with 
fludeoxyglucose (18F) examination must be reasonably documented. In case of 
chemotherapy regimen with cycles shorter than 4 weeks, the PET with fludeoxyglucose 
(18F) examination should be done just before re-starting a new cycle. 
 
In low-grade lymphoma, lower oesophagus cancer and suspicion of recurrent ovarian 
cancer, only positive predictive values have to be considered because of a limited 
sensitivity of PET with fludeoxyglucose (18F). 
 
Fludeoxyglucose (18F) is not effective in detecting brain metastases. 
The accuracy of fludeoxyglucose (
18F) PET imaging is better using PET/CT than PET 
cameras alone. 
When a hybrid PET-CT scanner is used with or without administration CT contrast media, 
some artefacts may occur on the attenuation-corrected PET images. 

Fluor-18-FDG, radioaktiv injektionsvæske 
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After the procedure  
Close contact with infants and pregnant women should be restricted during the initial 4 
hours following the injection. 
 
Specific warnings 
Depending on the time when you administer the injection, the content of sodium given to 
the patient may in some cases be greater than 1 mmol (23 mg). This should be taken into 
account in patient on low sodium diet. 
 
This medical product contains small amounts of ethanol (alcohol), less than 100 mg per 
dose. 
 
Precautions with respect to environmental hazard see section 6.6. 
 
4.5 
Interaction with other medicinal products and other forms of interaction 
All medicinal products that modify blood glucose levels can affect the sensitivity of the 
examination (e.g. corticosteroids, valproate, carbamazepine, phenytoin, phenobarbital and 
catecholamines). 
 
Under administration of colony-stimulating factors (CSFs), there is an increased uptake of 
fludeoxyglucose(18F) in the bone marrow and the spleen for several days. This must be 
taken into account for the interpretation of PET imaging. Separating CSF therapy from 
PET imaging by an interval of at least 5 days may diminish this interference. 
 
The administration of glucose and insulin influences the influx of fludeoxyglucose (18F) 
into the cells. In the case of high blood glucose levels as well as low plasma insulin levels, 
the influx of fludeoxyglucose (18F) into organs and tumours is reduced. 
18 
No formal studies on the interaction between fludeoxyglucose ( F) and any contrast for 
computed tomography have been performed 
4.6 
Pregnancy and lactation 
Pregnancy 
Women of childbearing potential 
When an administration of radiopharmaceuticals to a woman of childbearing potential is 
intended, it is important to determine whether or not she is pregnant. Any woman who has 
missed a period should be assumed to be pregnant until proven otherwise. If in doubt about 
her potential pregnancy (if the woman has missed a period, if the period is very irregular, 
etc.), alternative techniques not using ionising radiation (if there are any) should be offered 
to the patient. 
 
Pregnancy 
Radionuclide procedures carried out on pregnant women also involve radiation dose to the 
foetus. Only essential investigations should therefore be carried out during pregnancy, 
when the likely benefit far exceeds the risk incurred by the mother and foetus. 

Fluor-18-FDG, radioaktiv injektionsvæske 
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Breast-feeding 
Before administering radiopharmaceuticals to a mother who is breastfeeding consideration 
should be given to the possibility of delaying the administration of radionuclide until the 
mother has ceased breastfeeding, and to what is the most appropriate choice of 
radiopharmaceuticals, bearing in mind the secretion of activity in breast milk. If the 
administration is considered necessary, breastfeeding should be interrupted for 4 hours and 
the expressed feeds discarded. 
 
Close contact with infants should be restricted during the initial 4 hours following 
injection. 
 
Fertility  
No studies on fertility have been performed. 
 
4.7 
Effects on ability to drive and use machines 
Not relevant 
 
4.8 
Undesirable effects 
Exposure to ionising radiation is linked with cancer induction and a potential for 
development of hereditary defects. As the effective dose is 7.6 mSv when the maximal 
recommended activity of 400 MBq is administered these adverse reactions are expected to 
occur with a low probability. 
 
Reporting of suspected adverse reactions  
Reporting suspected adverse reactions after authorisation of the medicinal product is im- 
portant. It allows continued monitoring of the benefit/risk balance of the medicinal prod- 
uct. Healthcare professionals are asked to report any suspected adverse reactions via: 
 
Lægemiddelstyrelsen 
Axel Heides Gade 1 
DK-2300 København S 
Websted: www.meldenbivirkning.dk 
 
4.9 
Overdose 
In the event of administration of a radiation overdose with fludeoxyglucose ( 
 
18 
F) the 
absorbed dose to the patient should be reduced where possible by increasing the 
elimination of the radionuclide from the body by forced diuresis and frequent bladder 
voiding. It might be helpful to estimate the effective dose that was applied. 
 
5. 
PHARMACOLOGICAL PROPERTIES 
 
5.1 
Pharmacodynamic properties 
Pharmacotherapeutic group: Diagnostic radiopharmaceuticals, other diagnostic 
radiopharmaceuticals for tumour detection, ATC code V09IX04. 
 
Pharmacodynamic effects 
At the chemical concentrations used for diagnostic examinations, Fludeoxyglucose (18F) 
does not appear to have any pharmacodynamic activity. 

Fluor-18-FDG, radioaktiv injektionsvæske 
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5.2 
Pharmacokinetic properties 
Distribution 
Fludeoxyglucose (18F) is a glucose analogue, which is accumulated in all cells using 
glucose as primary energy source. Fludeoxyglucose (18F) is accumulated in tumours with a 
high glucose turnover. Following intravenous injection, the pharmacokinetic profile of 
Fludeoxyglucose (18F) in the vascular compartment is biexponential. It has a distribution 
time of 1 minute and an elimination time of approximately 12 minutes. 
18 
In healthy subjects, fludeoxyglucose ( F) is widely distributed throughout the body, 
particularly in the brain and heart, and to a lesser degree in the lungs and liver. 
 
Organ uptake 
The cellular uptake of Fludeoxyglucose (18F) is performed by tissue-specific carrier 
systems, which are partly insulin-dependent and, thus, can be influenced by eating, 
nutritional condition and the existence of a diabetes mellitus. In patients with a diabetes 
mellitus a reduced uptake of Fludeoxyglucose (18F) into the cells occurs due to a changed 
tissue distribution and glucose metabolism. 
 
Fludeoxyglucose (18F) is transported via the cell membrane in a similar fashion to glucose, 
but only undergoes the first step of glycolysis resulting in formation of Fludeoxyglucose 
(18F) -6-phosphate, which remains trapped within the tumour cells and is not further 
metabolised. Since the following dephosphorylation by intracellular phosphatases is slow, 
Fludeoxyglucose (18F) -6-phosphate is retained in the tissue over several hours (trapping 
mechanism). 
Fludeoxyglucose (18F) passes the blood-brain barrier. Approximately 7 % of the injected 
dose is accumulated in the brain within 80-100 minutes after injection. Epileptogenic foci 
exhibit a reduced glucose metabolism in the seizure free phases. 
Approximately 3 % of the injected activity is taken-up by the myocardium within 40 
minutes. The distribution of Fludeoxyglucose (18F) in normal heart is mainly homogenous; 
however, regional differences of up to 15 % are described for the interventricular septum. 
During and after a reversible myocardial ischemia, an increased glucose uptake occurs into 
the myocardial cell. 0.3 % and 0.9 - 2.4 % of the injected activity are accumulated in 
pancreas and lung. Fludeoxyglucose (18F) is also bound to a lesser extent to ocular muscle, 
pharynx and intestine. Binding to muscle may be seen following recent exertion and in the 
event of muscular effort during the examination 
Elimination 
Elimination of Fludeoxyglucose (18F) is chiefly renal, with 20 % of activity being excreted 
in urine in the first 2 hours following injection. Binding to renal parenchyma is weak, but 
because of renal elimination of Fludeoxyglucose (18F), the entire urinary system, 
particularly the bladder, exhibits marked activity. 
 
5.3 
Preclinical safety data 
Toxicological studies with mice and rats have demonstrated that with a single intravenous 
injection of 0.0002 mg/kg no deaths were observed. Toxicity with repeated administration 
was not performed because of Fludeoxyglucose (18F) is administered in a single dose. This 
medicinal product is not intended for regular or continuous administration. 
Mutagenicity studies and long-term carcinogenicity studies have not been carried out. 

Fluor-18-FDG, radioaktiv injektionsvæske 
Page 10 of 12 
 
6. 
PHARMACEUTICAL PARTICULARS 
 
6.1 
List of excipients 
Sodium citrate 
Di-sodium hydrogen citrate 1.5 hydrate 
Ethanol 
Sodium chloride 
Water for injections 
 
6.2 
Incompatibilities 
This medicinal product must not be mixed with other medicinal products except those 
mentioned in section 6.6. 
 
6.3 
Shelf life 
10 hours. 
 
6.4 
Special precautions for storage 
Do not store above 25°C. 
Do not freeze. 
 
Storage of radiopharmaceuticals should be in accordance with national regulations on 
radioactive materials. 
 
6.5 
Nature and contents of the container 
Two types of containers are used. Ph. Eur. Type I clear glass vials; 30 ml (only for internal 
use), and 10 ml vials, both sealed with a clear silicone rubber septum and aluminium crimp 
cap or Ph. Eur. Type I clear glass vials 10 ml sealed with a chlorobutyl rubber septum and 
aluminium crimp cap. 
The activity corresponds to 400 MBq to 210 GBq at time of calibration and is placed in a 
lead container. 
Multidose vial. 
Not all pack sizes may be marketed. 
 
6.6 
Special precautions for disposal and other handling 
 
General Warning 
Radiopharmaceuticals should be received, used and administered only by authorized 
persons in designated clinical settings. Their receipt, storage, use, transfer and disposal are 
subject to the regulations and/or appropriate licenses of the competent official organisation. 
 
Radiopharmaceuticals should be prepared by the user in a manner that satisfies both 
radiation safety and pharmaceutical quality requirements. Appropriate aseptic precautions 
should be taken. 
The solution may be diluted with sodium chloride 9 mg/ml (0.9 %) solution for injection. 
 
The administration of radiopharmaceuticals creates risks for other people from external ra- 
diation or contamination from spills of urine, vomiting etc. Radiation protection precau- 
tions in accordance with national regulations must be taken. 

Fluor-18-FDG, radioaktiv injektionsvæske 
Page 11 of 12 
 
Any unused medicinal product or waste material should be disposed of in accordance with 
local requirements. 
 
7. 
MARKETING AUTHORISATION HOLDER 
Cyklotron og Radiokemi, enhed 3982 
Afdeling for Klinisk Fysiologi og Nuklear Medicin 
Rigshospitalet 
Blegdamsvej 9, 
DK-2100 Copenhagen Ø 
 
8. 
MARKETING AUTHORISATION NUMBER 
DK R 14 
 
9. 
DATE OF FIRST AUTHORISATION 
28 May1999 
 
10. 
DATE OF REVISION OF THE TEXT 
20 March 2024 
 
11. 
DOSIMETRY 
The data listed below are from ICRP 106 Publication. 
 
Organ 
Absorbed dose per unit activity administered (mGy/MBq) 
Adult 
15 yrs old 
10 yrs old 
5 yrs old 
1 yr old 
Adrenal 
0.012 
0.016 
0.024 
0.039 
0.071 
Bladder 
0.13 
0.16 
0.25 
0.34 
0.47 
Bone surfaces 
0.011 
0.016 
0.022 
0.034 
0.064 
Brain 
0.038 
0.039 
0.041 
0.046 
0.063 
Breasts 
0.0088 
0.011 
0.018 
0.029 
0.056 
Gallbladder 
0.013 
0.016 
0.024 
0.037 
0.070 
Gastrointestinal 
tract 
Stomach 
0.011 
0.014 
0.022 
0.035 
0.067 
Small 
intestine 
0.012 
0.016 
0.025 
0.040 
0.073 
Colon 
0.013 
0.016 
0.025 
0.039 
0.070 
(ULI wall 
0.012 
0.015 
0.024 
0.038 
0.070) 
(LLI wall 
0.014 
0.017 
0.027 
0.041 
0.070) 
Heart 
0.067 
0.087 
0.13 
0.21 
0.38 
Kidneys 
0.017 
0.021 
0.029 
0.045 
0.078 
Liver 
0.021 
0.028 
0.042 
0.063 
0.12 
Lungs 
0.020 
0.029 
0.041 
0.062 
0.12 
Muscles 
0.010 
0.013 
0.020 
0.033 
0.062 
Oesophagus 
0.012 
0.015 
0.022 
0.035 
0.066 
Ovaries 
0.014 
0.018 
0.027 
0.043 
0.076 
Pancreas 
0.013 
0.016 
0.026 
0.040 
0.076 
Red marrow 
0.011 
0.014 
0.021 
0.032 
0.059 
Skin 
0.0078 
0.0096 
0.015 
0.026 
0.066 

Fluor-18-FDG, radioaktiv injektionsvæske 
Page 12 of 12 
 
Spleen 
0.011 
0.014 
0.021 
0.035 
0.066 
Testes 
0.011 
0.014 
0.024 
0.037 
0.066 
Thymus 
0.012 
0.015 
0.022 
0.035 
0.066 
Thyroid 
0.010 
0.013 
0.021 
0.034 
0.065 
Uterus 
0.018 
0.022 
0.036 
0.054 
0.090 
Remanining 
organs 
0.012 
0.015 
0.024 
0.038 
0.064 
Effective dose 
(mSv/MBq) 
0.019 
0.024 
0.037 
0.056 
0.095 
 
The effective dose resulting from the administration of a maximal recommended activity 
of 400 MBq of fludeoxyglucose (18F) for an adult weighing 70 kg is about 7.6 mSv. 
For an administered activity of 400 MBq, the typical radiation doses delivered to the 
critical organs, bladder, heart and brain are: 52 mGy, 27 mGy and 15 mGy, respectively. 
 
12. INSTRUCTIONS FOR PREPARATION OF RADIOPHARMACEUTICALS 
Method of preparation 
The package must be checked before use and the activity measured using an activimeter. 
The medicinal product may be diluted with sodium chloride 9 mg/mL solution for injec- 
tion. 
Withdrawals should be performed under aseptic conditions. The vials must not be opened 
before disinfecting the stopper, the solution should be withdrawn via the stopper using a 
single dose syringe fitted with suitable protective shielding and a disposable sterile needle 
or using an authorised automated application system. 
If the integrity of this vial is compromised, the product should not be used. 
 
Quality control  
The solution should be inspected visually prior to use. Only clear solutions, free of visible 
particles should be used. 

1 
 
 
 
 
 
 
 
 
October 2024 
Version 2.0 
T +45 4488 9123 
E kf@dkma.dk 
 
The Danish Medicines Agency’s guidance on risk-based recording and 
reporting of adverse events in clinical trials on medicinal products 
under Regulation (EU) no. 536/2014 
 
 
 
Table of contents 
1. 
Introduction ................................................................................................................................................................. 2 
2. 
Requirements in relation to risk adaptation in adverse event management ................................................................ 3 
3. 
Process for assessing adverse events in a clinical trial ............................................................................................... 4 
4. 
Risk assessment of a clinical trial ............................................................................................................................... 6 
5. 
Risk-adapted adverse event management in a clinical trial ........................................................................................ 8 
6. 
Appendix ................................................................................................................................................................... 11 
Appendix 1 – Assessment of events and adverse reactions in a clinical trial ................................................................ 11 
Appendix 2 – Description of selected terms .................................................................................................................. 12 
Appendix 3 – General considerations about risk factors and risk minimisation measures ............................................. 14 
Appendix 4 – Examples of clinical trials at the different risk levels ................................................................................ 15 
Appendix 5 – Evidence generation and data sources for authorised medicinal products .............................................. 16 
7. 
Change log ............................................................................................................................................................... 18 

2 
 
 
 
 
 
 
1. Introduction 
The recording and reporting of adverse events is a critical process for safeguarding the safety of participants 
in a clinical trial and essential for ensuring the evidence and accuracy of a medicinal product’s safety profile. 
However, it is acknowledged that the collection and reporting of adverse events can be resource-consuming 
for both the investigator and sponsor and therefore should be risk-adjusted based on the added value gained 
from collecting the adverse event data. 
Detailed recording of adverse events is particularly important for medicinal products that are not yet 
authorised, and where the data on the medicinal product’s safety profile are insufficient. In contrast, clinical 
trials involving well-established authorised medicinal products contribute less with new significant safety 
data. 
Article 41(2) of the legislation on clinical trials with medicinal products, regulation (EU) No 536/2014 of 16 
April 2014 (CTR)1 allows adaptation of adverse event management2 in relation to the individual protocol: 
 
 
 
In practice, this means that the clinical trial adverse event management can be adapted based on the trial’s 
specific design and purpose. Risk adaptation of adverse event management must be solid justified within the 
protocol with patient safety and the integrity of trial data remaining as the top priorities. 
This guidance describes the requirements and processes needed for implementing risk-adapted adverse 
event management. 
In the case of clinical trials serving a regulatory purpose (e.g. an indication extension or marketing 
authorisation), reference is also made to the ICH guideline E19 on a selective approach to safety data 
collection in specific late-stage pre-approval or post-approval clinical trials3. 
 
 
 
 
1 More information about the clinical trials regulation is provided on the website of the Danish Medicines Agency. 
2 The term ‘adverse event management’ will be used in this guidance document as a collective term for recording and 
reporting of adverse events. 
3 ICH guideline E19 on a selective approach to safety data collection in specific late-stage pre-approval or post- 
approval clinical trials is available on the European Medicines Agency’s website. 
REGULATION (EU) No 536/2014 of 16 April 2014 on clinical trials on medicinal products for human use: 
 
CHAPTER VII, Article 41(2): 
“The investigator shall record and document all adverse events, unless the protocol provides differently. The investigator shall 
report to the sponsor all serious adverse events occurring to subjects treated by him or her in the clinical trial, unless the protocol 
provides differently. 
The investigator shall report serious adverse events to the sponsor without undue delay but not later than within 24 hours of 
obtaining knowledge of the events, unless, for certain serious adverse events, the protocol provides that no immediate 
reporting is required. Where relevant, the investigator shall send a follow-up report to the sponsor to allow the sponsor to 
assess whether the serious adverse event has an impact on the benefit-risk balance of the clinical trial.” 

3 
 
 
 
For general considerations on the risk assessment of clinical trials, please refer to the Risk proportionate 
approaches in clinical trials - Recommendations of the expert group on clinical trials for the implementation 
of Regulation (EU) No 536/2014 on clinical trials on medicinal products for human use (25 April 2017)4. 
 
 
 
2. Requirements in relation to risk adaptation in adverse event management 
Sponsors intending to apply any risk adaptation in adverse event management in clinical trials should pay 
attention to the following: 
1. Any risk-adapted adverse event management must be justified in relation to the specific trial’s 
purpose, design and risk assessment. The protocol must include a clear justification along with a 
detailed description of the risk-based approaches, including a description of the processes in place 
for adverse event management. Guidance on these areas is given in the following sections: 
➢ Process for assessing adverse events in a clinical trial (section 3) 
➢ Risk assessment of a clinical trial (section 4) 
➢ Risk-adapted adverse event management in a clinical trial (section 5) 
 
2. The sponsor must establish whether the medicinal products included in a clinical trial are subject to 
stricter national reporting requirements and/or additional monitoring in the EU. Risk adaptation is 
usually not possible for authorised medicinal products subject to stricter reporting requirements or 
additional monitoring. In case of risk-adapted adverse event management, the sponsor must confirm 
in the protocol that the medicinal products in a clinical trial are not subject to stricter national 
reporting requirements in the concerned Member States involved in the clinical trial or additional 
monitoring in the EU. The medicinal products subject to stricter reporting requirements in Denmark 
is available in the list published by the Danish Medicines Agency. The list of medicines under 
additional monitoring in the EU is available on the European Medicines Agency's website. 
3. Risk-adapted adverse event management may only be implemented in relation to the recording and 
reporting of adverse events and adverse reactions from investigator to sponsor. For information 
about the sponsor’s reporting obligations, reference is made to the requirements of the CTR5. 
4. Clinical trials investigating diseases with high morbidity or mortality may have primary or secondary 
efficacy endpoints that fall under the definition of a suspected unexpected serious adverse reaction 
(SUSAR). In such trials, according to CTR Annex III, section 2.5 point (21), it may be justified to 
designate specific serious events as disease-related and exempt them from SUSAR obligations. This 
in order to avoid systematic unblinding and to maintain the integrity of the trial data. In such cases, 
a Data Safety Monitoring Board (DSMB) should be established to monitor unblinded data. If a DSMB 
is not established, it must be justified how continuous safety monitoring is ensured in some other 
way. It may also be justified to exempt the same serious events from immediate reporting by the 
investigator to the sponsor. However, this requires an alternative procedure to ensure that the DSMB 
has continuous access to complete safety data. 
 
4 Risk proportionate approaches in clinical trials - Recommendations of the expert group on clinical trials for the 
implementation of Regulation (EU) No 536/2014 on clinical trials on medicinal products for human use (25 April 2017) 
is available at EudraLex - Volume 10 - Clinical trials guidelines. 
5 The sponsor’s obligations in relation to reporting to the authorities are provided in articles 42 and 43 of CTR 
536/2014. 

4 
 
 
 
 
5. The annual safety report (ASR) must describe the risk-adapted approaches under which the ASR has 
been prepared. The sponsor is obligated to include all serious adverse reactions (SARs) and all 
suspected unexpected serious adverse reactions (SUSARs) in the ASR. If there are exemptions to 
immediate reporting of serious adverse events to the Sponsor, it is important to note that all 
registered serious adverse events must still be reported to the sponsor, in a timely manner, for the 
sponsor to include all the registered serious events in the ASR. The protocol must also state if a single 
safety report is submitted for all investigational medicinal products used in the clinical trial, see article 
43(2) of the CTR. 
 
6. Adverse events exempted from recording are not expected to be documented elsewhere. However, 
the investigator remains responsible for ensuring that the trial participants’ medical records are 
continuously updated with clinically relevant information for healthcare professionals who are 
otherwise involved in the patients’ present or future care and treatment. During GCP-inspections 
particular attention may be given to how medical records entries are handled. 
The protocol template published by the Danish Medicines Agency can be used to prepare the protocol. The 
template describes the particulars to be included in the protocol for compliance with the CTR. 
 
 
 
3. Process for assessing adverse events in a clinical trial 
It is essential for the safety of trial participants and the data integrity, that the sponsor, investigator and other 
relevant staff understand and have received training in the processes for assessment, recording and reporting 
of adverse events. The processes for assessment of adverse events and the definitions of relevant terms must 
therefore be sufficiently described in the protocol. 
The process for assessing whether it is a serious adverse event (SAE), a serious adverse reaction (SAR) or a 
suspected unexpected serious adverse reaction (SUSAR) is described below (Figure 1). You will find the full 
flow chart for assessment of all events in Appendix 1 and a description of relevant terms in Appendix 2. 
These processes must be in place irrespective of whether risk-adapted recording and reporting of adverse 
events is implemented. 
 
 
Figure 1. Assessment of serious adverse events and adverse reactions. 
 
SAE (serious adverse event) 
A serious adverse event (SAE) means any untoward medical occurrence that at 
any dose requires inpatient hospitalisation or prolongation of existing 
hospitalisation, results in persistent or significant disability or incapacity, results 
in a congenital anomaly or birth defect, is life-threatening, or results in death. 

5 
 
 
 
 
 
 
 
 
 
Annual safety reports must be prepared and reported for all trials 
Once a year, the sponsor must summarise cumulative safety information in the annual safety report. Based 
on this report, the safety of the trial is evaluated, including if the benefit-risk balance has changed and 
whether, on the basis thereof, the trial may continue. The annual safety report ensures the continuous safety 
assessment and may therefore not be exempted despite any applied risk-adapted adverse events 
management. 
The annual safety report must describe the risk-adapted approaches as provided in the clinical trial protocol, 
under which the report has been prepared. 
Causality assessment – is the serious adverse event related to the investigational 
medicinal product? 
In determining whether an adverse event is an adverse reaction, consideration 
shall be given to whether there is a reasonable possibility of establishing a causal 
relationship between the event and the investigational medicinal product (IMP) 
based on an analysis of available evidence. 
See the reference provided in Appendix 2 for guidance on the causality 
assessment 
SAR (serious adverse reaction) 
A serious adverse reaction (SAR) is an SAE that is assessed to be related to the 
IMP, i.e. the treatment administered in the clinical trial. 
Is the serious adverse reaction expected or unexpected? 
The determination of whether an event is expected or unexpected is assessed 
based on the reference safety information (RSI). 
Example: In the case of authorised medicinal products, the RSI is often section 
4.8 of the summary of product characteristics (SmPC). Therefore, an adverse 
reaction appearing in the SmPC section 4.8 is expected, and an adverse reaction 
not appearing in section 4.8 of the SmPC is unexpected. 
SUSAR (suspected unexpected serious 
adverse reaction) 
A suspected unexpected serious adverse reaction means a serious adverse 
reaction, the nature, severity or outcome of which is not consistent with the RSI. 
ASR (annual safety report) 
Annual safety report: It is expected that any relevant safety information will be 
described in the annual safety report. The report is expected to include a list of 
SARs and SUSARs and an assessment of whether these events give rise to 
updating the protocol. 
Likewise, the annual safety report is expected to include an assessment of 
whether the benefit-risk balance is changed or unchanged, meaning if the trial 
may continue or if a protocol amendment is required for it to continue. 

6 
 
 
 
 
4. Risk assessment of a clinical trial 
The level needed for adverse event recording and reporting depends on the evidence base of the investigated 
medicinal product. As mentioned earlier, risk-adapted adverse event management must be justified on the 
basis of a trial-specific risk assessment. 
A risk assessment means the identification of potential risks associated with the concerned trial, based on 
the safety of the participants, the investigational medicinal product and the trial design and methods. A 
number of different factors influence the extent to which the safety of the trial participants is affected in the 
trial, e.g. the status, type and safety profile of the medicinal product, the difference between intervention 
and normal clinical practice, and the complexity of the trial. The risk assessment and the associated risk 
categorisation of a trial are described below in Figure 2, points 1-4. 
 
 
Figure 2. Risk assessment of a trial for the purpose of applying risk-adapted adverse event management. 
 
 
1) 
Consider the RISK FACTORS likely to impact the safety of the trial participant 
At least the following points must be considered and addressed in a risk assessment: 
➢ 
Whether the medicinal product is authorised, including the total exposure of the medicine and whether the available safety 
data of the medicinal product provides sufficient grounds to implement risk-adapted adverse event management. 
➢ 
The type of medicinal product/intervention (e.g. mechanistic characteristics, pharmaceutical form, route of administration). 
➢ 
Indication, including the difference between intervention and normal clinical practice. 
➢ 
Population, including age, gender and other patient characteristics. 
➢ 
Dose and treatment regimen compared to the authorised dose and treatment regimen described in the product 
information, including the use of combination therapy or other medicines given concurrently, including an assessment of 
whether this may lead to serious or more frequent adverse reactions, new adverse reactions or new drug interactions. 
➢ 
Complexity of the trial design. 
See Appendix 3 for more considerations of risk factors likely to impact the safety of trial participants. 

7 
 
 
 
2) 
Assess the RISK LEVEL based on the difference between intervention and normal clinical practice 
What is the risk posed to the patient compared to the standard treatment? 
What are the risks, and how can they be handled? 
INCREASED RISK FOR PATIENTS 
“Low-risk” trial = risk level 1 
➢ 
The investigational medicinal 
product(s) is/are authorised 
➢ 
The intervention is comparable 
to standard treatment 
➢ 
The intervention and the 
medicinal product’s evidence 
base and safety profile are 
robust, also in relation to rare 
adverse reactions 
➢ 
Expected new signals are 
minimal 
Application of risk-adapted adverse 
event management can generally be 
justified. 
See examples in Appendix 4. 
“Medium-risk” trial = risk level 2 
➢ 
The investigational medicinal product(s) 
are authorised, but are used for an 
unapproved indication 
➢ 
The intervention is not significantly 
different from the standard treatment, 
and the safety profile is expected to be 
comparable 
➢ 
The safety profile of the medicinal 
product is robust 
Application of risk-adapted adverse event 
management can be justified if based on a 
trial-specific risk assessment. 
The risk assessment and justification should 
address the risk factors listed under point 1) 
of this figure. 
See examples in Appendix 4. 
“High-risk” trial = risk level 3 
➢ 
Investigational medicinal product 
or indication is not authorised 
➢ 
The intervention has not been 
studied before or is significantly 
different from the standard 
treatment 
➢ 
The intervention and the safety 
profile of the medicinal product 
have not been sufficiently 
studied, and evidence on the 
efficacy and safety of the product 
is insufficient 
➢ 
The investigational medicinal 
product is authorised but subject 
to stricter national reporting 
requirements or additional 
monitoring. See point 2 in section 
2. 
Thorough adverse event management 
is needed to safeguard patient safety 
and to ensure the collection of data on 
the safety profile of the medicinal 
product. 
Full adverse event management is 
expected, unless adaptation can be 
justified on robust grounds based on a 
trial-specific risk assessment. 
See examples in Appendix 4. 
 

8 
 
 
 
 
 
 
 
 
5. Risk-adapted adverse event management in a clinical trial 
In general, all adverse events must be recorded and all serious adverse events must be reported to the 
sponsor, unless the risk-adapted adverse event management is supported by the risk assessment 
documented in the protocol. 
Authorised medicinal products have generated a sufficient evidence base for their use with respect to the 
populations and indications as described in the SmPC, and the safety of authorised medicinal products is 
monitored on an ongoing basis (see Appendix 5). In relation to clinical trials with authorised medicinal 
products, it may therefore be possible to adapt recording and reporting of adverse events proportionate to 
the risk level of the trial. Conversely, it can usually not be justified to reduce the recording and reporting of 
adverse events for trials with non-authorised medicinal products. 
3) 
Assess if risk-adapted adverse event management may be justified 
Based on the above risk assessment, a risk-adapted approach to recording and reporting of adverse events may be possible if 
sufficiently justified. 
Even so, borderline cases may exist, which means that an assessment of the individual protocol and trial design is needed to 
determine the required level of adverse event management. In borderline cases, variables like the duration of treatment, whether 
or not a life-threatening disease is involved, knowledge of the product’s mechanistic effects, as well as non-clinical signals, along 
with data from the clinical development and the total exposure of the medicinal product, may determine which approach is 
justifiable. This must be seen in the context of the robustness of the safety profile, also in relation to rare adverse events. 
If there are doubts about whether the evidence base of the product’s safety is sufficiently known or whether the intervention may 
expose the patient to a risk, conservative/full adverse event management must be applied. 
See section 5 on risk adaptation in the management of adverse events. 
4) 
Dedicate a section in the protocol specifically to the justification of risk-adapted adverse event management 
This justification must at least include the following: 
➢ 
Risk assessment of the trial and justification of the level of risk chosen for the trial. 
➢ 
Description of risk-adapted adverse event management, including reasons why certain SAEs are not be recorded or 
not immediate reported to the sponsor. 
➢ 
Considerations about the risks associated with the chosen risk-adapted adverse event management: 
o 
For trial participants? 
o 
For data integrity? 
➢ 
How risks in the trial can be prevented and/or reduced? 
The extent of the justification depends on the level of risk associated with the trial. 

9 
 
 
 
The protocol must always provide justification for any risk-adapted approach on the basis of a trial-specific 
risk assessment and if there is a risk of new, more serious or more frequent adverse reactions. Regardless of 
the selected approach, the investigator must always have the possibility of recording any event and reporting 
these to the sponsor if the investigator finds this relevant/necessary. 
The possibility of applying a risk-adapted approach to the recording and reporting of adverse events and 
adverse reactions from investigator to sponsor is described below in Table 1 and Tabel 2. SUSARs must always 
be reported by the sponsor to the EudraVigilance database regardless of the risk-adaptation applied to 
adverse event management, as stipulated in the CTR6. Likewise, the sponsor is required to submit annual 
safety reports (ASRs) via CTIS7. 
Table 1. Risk-adapted adverse event management based on the level of risk associated with the trial 
 
Risk level: 
Risk level 1 = “Low” 
Risk level 2 = “Medium” 
Risk level 3 = “High” 
Recording of adverse events 
Is risk-adaptation for AE 
recording possible? 
YES 
– AE recording can be 
exempted 
YES 
– AE recording can be exempted 
NOb) 
– all AEs must be recorded 
Is risk-adaptation for SAE 
recording possible? 
YES 
– SAE recording can be 
exempted 
YESa) 
– SAEs pursuant to a predefined 
list in the protocol can be 
exempted from recording 
NOb) 
– all SAEs must be recorded 
Is risk-adaptation for SAR 
recording possible? 
YES 
– only suspected unexpected 
serious adverse reactions 
(SUSARs) must be recorded 
YESa) 
– SARs pursuant to a predefined 
list in the protocol can be 
exempted from recording 
NOb) 
– all SARs must be recorded 
Reporting of serious adverse events from investigator to sponsor 
Is risk-adaptation for SAE 
reporting to sponsor possible? 
YES 
– SAE reporting can be 
exempted 
YESa) 
– immediate reporting of 
recorded SAEs can be exempted, 
but must be reported to the ASR 
NOb) 
– all SAEs must be reported 
immediately to sponsor 
Is risk-adaptation for SAR 
reporting to sponsor possible? 
YES 
– only suspected unexpected 
serious adverse reactions 
(SUSARs) must be reported 
immediately to sponsor 
NOb) 
– all recorded SARs must be 
reported immediately to sponsor 
NOb) 
– all SARs must be reported 
immediately to sponsor 
Sponsor’s reporting obligations 
SUSAR reporting 
SUSARs must always be reported by the sponsor to the EudraVigilance database. 
Annual safety report (ASR) 
The ASR must always be submitted by the sponsor via CTIS. See also section 3. 
a) Must always be justified based on the trial-specific risk assessment 
b) Generally not possible, unless robust justification provided 
 
 
6 Find more information about reporting to the EudraVigilance database on the website of the Danish Medicines 
Agency. 
7 Clinical Trials Information System (https://euclinicaltrials.eu/) 

10 
 
 
 
Tabel 2. Description of risk-adapted adverse event management. 
 
Description of risk-adapted adverse event management based on the risk level 
Adverse event management at 
risk level 1: 
The investigator must at least record adverse events satisfying all the following three criteria: 
1) 
The adverse event must be serious (serious adverse event, SAE) 
2) 
The adverse event must be suspected to be related to the investigational medicinal product 
(serious adverse reaction, SAR) 
3) 
The adverse event must not appear in section 4.8 of the summary of product 
characteristics. 
In reality, it is the investigator who must assess expectedness when only suspected unexpected 
serious adverse reaction (SUSARs) are to be recorded. 
The investigator must report all recorded adverse reactions (subject to the above requirements) to 
the sponsor within 24 hours. 
The investigator must always have the possibility of recording and reporting any event to the sponsor 
if the investigator finds this relevant/necessary and this must be stated in the protocol. 
Adverse event management at 
risk level 2: 
In general, all SAEs must be recorded, but the sponsor may include in the protocol a predefined list of 
SAEs not to be recorded. This could be SAEs either associated with the investigational medicinal 
product or an underlying disease. SAEs in this category could be administrative/planned 
hospitalisation, exacerbation of underlying disease, or in the case of the treatment of intensive-care 
patients expected to have a critical disease course involving, for example, multiple organ failure. 
SAEs that are related to the investigational medicinal product (=SARs) and are listed in section 4.8 of 
the product information (known adverse reactions) may generally be exempted from recording. In 
case of that other SARs than expected (known adverse reactions, see 4.8 of the product information) 
will be exempted from recording, this must be further justified. 
Any SAEs and/or SARs exempted from the recording must always be clearly stated and justified in the 
protocol. 
The reporting of SAEs to the sponsor within 24 hours can be omitted, if predefined in the protocol 
and justified. However, all SAEs recorded and deemed related to the intervention (causal 
relationship) must be reported immediately to the sponsor. In other words, all recorded SARs must 
be reported to the sponsor within 24 hours. 
If SARs are exempted from immediate reporting due to the fact that they are recorded as part of the 
clinical trial’s primary or secondary efficacy endpoints, continuous safety monitoring must be ensured 
through a DSMB. Please see point 4 in section 2. 
For SAEs exempted from immediate reporting, it is important to note that all SAEs recorded but not 
reported immediately, must still be reported to the sponsor no later than before preparation of the 
ASR, and the specific frequency of reporting must be stated and justified in the protocol. 
The investigator must always have the possibility of recording and reporting any event to the sponsor 
if the investigator finds this relevant/necessary and this must be stated in the protocol. 
Adverse event management at 
risk level 3: 
It is expected that all AEs/SAEs are recorded, and that all SAEs/SARs are reported to the sponsor 
within 24 hours. Risk-adaptation is in general not possible, unless the sponsor can provide a robust 
justification based on a trial-specific risk assessment. 

11 
 
 
 
 
6. Appendix 
Appendix 1 – Assessment of events and adverse reactions in a clinical trial 
 
 
Seriousness 
assessment 
 
Serious 
Not serious 
 
 
 
 
 
 
Causality assessment  
Related to 
investigational 
medicinal 
product (IMP) 
 
Related to 
investigational 
medicinal product 
(IMP) 
 
 
 
 
 
 
 
 
 
Expected 
Serious adverse reaction (SAR) 
 
Expected vs. 
unexpected 
(expectedness) 
assessment 
 
Unexpected 
Suspected unexpected serious adverse reaction 
(SUSAR) 
It is a SUSAR if the answer is yes to all the following questions: 
– Serious event? 
– Related to IMP? 
– Unexpected (in relation to RSI)? 
Adverse Event (AE) 
Serious adverse event (SAE) 
Adverse event (AE) 
Serious 
adverse 
reaction (SAR) 
Serious adverse 
event (SAE) 
Adverse reaction 
(AR) 
Adverse event 
(AE) 
Not related 
Not related 

12 
 
 
 
 
Appendix 2 – Description of selected terms 
Adverse event (AE): 
Any untoward medical occurrence in a subject to whom a medicinal product is administered and which does 
not necessarily have a causal relationship with this treatment. 
 
 
Seriousness criteria: 
The event is serious if at least one of the following criteria applies: 
- 
inpatient hospitalisation or prolongation of existing hospitalisation 
- 
results in persistent or significant disability or incapacity 
- 
results in a congenital anomaly or birth defect 
- 
is life-threatening 
- 
results in death 
 
Serious adverse event (SAE): 
Any untoward medical occurrence that at any dose requires inpatient hospitalisation or prolongation of 
existing hospitalisation, results in persistent or significant disability or incapacity, results in a congenital 
anomaly or birth defect, is life-threatening, or results in death. 
 
 
Causality assessment: 
A causality assessment is used to assess if an event is related to investigational medicine/intervention or not. 
In determining whether an adverse event is an adverse reaction, consideration shall be given to whether there 
is a reasonable possibility of establishing a causal relationship between the event and the investigational 
medicinal product based on an analysis of available evidence. 
In the absence of information on causality provided by the reporting investigator, the sponsor shall consult 
the reporting investigator and encourage him to express an opinion on this issue. The causality assessment 
given by the investigator shall not be downgraded by the sponsor. If the sponsor disagrees with the 
investigator's causality assessment, the opinion of both the investigator and the sponsor shall be provided 
with the report. 
The WHO-UMC’s method may be used to make the causality assessment: 
https://www.who.int/docs/default-source/medicines/pharmacovigilance/whocausality-assessment.pdf 
 
 
Serious adverse reaction (SAR): 
Is an SAE in which the event is assessed to be related (see causality assessment) to the investigational 
medicine and/or intervention. 

13 
 
 
 
 
Suspected unexpected serious adverse reaction (SUSAR): 
A serious adverse reaction, the nature, severity or outcome of which is not consistent with the reference safety 
information. Whether an incident is unexpected or expected is determined based on the reference safety 
information. 
 
 
Reference safety information (RSI): 
The determination of whether an event is expected or unexpected is assessed in relation to the reference 
safety information (RSI). Often, parts of the product information or parts of the Investigator's Brochure (IB) 
are used as RSI for the investigational medicinal product. 
Example: 
In the case of authorised medicinal products, the RSI is often a part of the summary of product characteristics 
(SmPC), i.e. an adverse reaction appearing in the SmPC, often section 4.8, is expected; an adverse reaction 
not appearing in the product information is unexpected. 
 
 
Annual safety report (ASR): 
Any relevant safety information is expected to be described in the annual safety report. A list of SARs and 
SUSARs is expected, including an assessment of whether these events give rise to updating the protocol. 
The annual safety report must describe the risk-adapted approaches subject to which it has been prepared. 
Likewise, the annual safety report is expected to include an assessment of whether the benefit-risk balance 
has changed or is unchanged, meaning if the trial may continue or if protocol amendments are required for it 
to continue. 
It is possible to submit a single safety report on all investigational medicinal products used in a clinical trial, 
see article 43(2) of the CT regulation. 

14 
 
 
 
 
Appendix 3 – General considerations about risk factors and risk minimisation measures 
The following may be considered in connection with the risk assessment (list is non-exhaustive): 
• 
Does the trial population consist of healthy trial subjects or patients? 
 
• 
Is the investigational medicinal product authorised, and is it used in compliance with what has been 
approved and described in the product information? If not, consider the following: 
➢ Are there changes to the dosage regime/route of administration? 
➢ Are there changes to the population/indication? 
➢ How will these changes impact the safety of trial participants? 
 
• 
What are the known/expected risks, both in relation to the trial design and/or the investigational 
medicinal product? 
➢ Have these risks been addressed in normal clinical practice? 
➢ If the adverse reaction profile of the investigational medicinal product is unknown, which 
risks are expected based on non-clinical data and/or based on the knowledge from other 
medicinal products containing the same active substance? 
➢ Is the duration of treatment supported by previous experience? 
➢ Is there a risk of dosing errors? 
 
• 
Are there any risks of interactions with other treatments given concurrently that could increase the 
risk to trial participants? 
 
• 
Is there a need for further safety monitoring of the trial participant in addition to that provided in 
standard treatment? This could be additional laboratory tests, ECG, imaging, biopsy, more frequent 
visits to the doctor. 
 
• 
Are further risk minimisation measures needed? The following may be considered: 
➢ Restrictive inclusion and exclusion criteria, e.g. exclusion of persons with a particular risk due 
to secondary diseases, resulting from impaired kidney/lung/heart/liver function or the use of 
certain medicinal products. 
➢ Adjustment of treatment regimen and duration, including sufficient monitoring and facilities, 
rescue medicine and the presence of trained (emergency) staff when relevant. 
➢ Stopping criteria or (dose) modification of the investigational treatment, e.g. using a 
protocol-specified treatment algorithm or an independent Data Safety Monitoring Board 
(DSMB). 
➢ Focused recording of adverse events and adverse reactions, e.g. organ-specific events or 
events giving cause for specific concern; reporting to the sponsor and authorities must comply 
with the legislative requirements at all times. 
➢ Further safety monitoring, e.g. by way of experts in the disease, in its routine treatment and 
in the investigational medicinal product/study treatment; an independent DSMB for the 
assessment of new safety data and benefit-risk balance. 

15 
 
 
 
 
Appendix 4 – Examples of clinical trials at the different risk levels 
 
 
 
 
 
8 Under article 2(3) of the CTR, a low-intervention clinical trial is a clinical trial which fulfils all the following conditions: 
a. 
the investigational medicinal products, excluding placebos, are authorised; 
b. according to the protocol of the clinical trial, i) the investigational medicinal products are used in accordance 
with the terms of the marketing authorisation; or ii) the use of the investigational medicinal products is 
evidence-based and supported by published scientific evidence on the safety and efficacy of those 
investigational medicinal products in any of the Member States concerned; and 
c. 
the additional diagnostic or monitoring procedures do not pose more than minimal additional risk or burden 
to the safety of the subjects compared to normal clinical practice in any Member State concerned; 
9 Including authorised medicinal products subject to additional monitoring and stricter reporting requirements 
Examples “low-risk” trials (risk level 1): 
•
Low-intervention trials8 
•
Trials with authorised medicinal products involving an approved indication in which the intervention is 
normal clinical practice. 
•
Trials with authorised medicinal products involving a well-established off-label indication which is 
normal clinical practice and supported by published evidence. 
Examples of “medium-risk” trials (risk level 2): 
•
Trials with authorised medicinal products involving an unapproved indication in which the studied 
indication/population/treatment DOES NOT differ significantly from the authorised indication or 
normal clinical practice, and where the safety profile is expected to be the same. 
•
PK/PD trials with data available from other authorised medicinal products in the same pharmacological 
class. 
Examples of “high-risk” trials (risk level 3): 
•
Trials with non-authorised medicinal products or authorised medicinal products with limited knowledge 
about adverse reactions9. 
•
Trials with authorised medicinal products involving an unapproved indication in which the studied 
indication differs significantly from the approved one, e.g. another disease area or a special population 
such as children for which the safety profile of the intervention has not been established despite the 
status of the medicinal product. 
•
Trials with combination treatment with two or more medicinal products, posing a risk of drug 
interactions and where it is not possible to break down the adverse event management on the 
individual medicinal products. 
•
Trials with modified medicinal products without a marketing authorisation, for example a new 
formulation/pharmaceutical form. 
•
Trials in which the medicinal product is used in combination with medical devices or other medicinal 
products with an expected synergistic effect (e.g. electroporation). 

16 
 
 
 
 
Appendix 5 – Evidence generation and data sources for authorised medicinal products 
Medicinal products used in clinical trials are categorised as investigational medicinal products whether or not 
they have a marketing authorisation. Consequently, adverse event data collected in a clinical trial are not 
automatically sent to the marketing authorisation holder. Instead, alternative mechanisms ensure that the 
marketing authorisation holder can gain a complete overview of emerging safety data. One such mechanism 
is the sponsor’s ongoing reporting of SUSARs to EudraVigilance database which are searchable by the 
marketing authorisation holder. Another mechanism is the literature searches made by the marketing 
authorisation holder which aim to identify publications containing safety data related to the concerned 
medicinal product (Figure 3). 
 
 
Figure 3 Safety data sources for authorised medicinal products 
 
 
 
As illustrated in the figure above, literature searches will also identify adverse reaction data from other 
sources, such as registry-based studies. This reveals a complex array of data sources that collectively provide 
a comprehensive evidence base for the safety of the medicinal product. 
Each source of adverse reaction data has its advantages and disadvantages concerning the quality of the 
evidence it provides, emphasising the importance of all data sources in enhancing the knowledge about 
pharmaceutical safety. Spontaneous reports related to authorised medicinal products generate a substantial 
volume of data. However, the lack of background frequencies is a significant disadvantage compared to 
controlled clinical trials, where frequency comparison is possible. While registry studies allow for such 
comparisons, they lack the medical causality assessment that are conducted for each recorded adverse event 
in a clinical trial (Figure 4). 
Where the array of data sources is complex when it comes to authorised medicinal products, the sole source 
of evidence is clinical trials when it comes to non-authorised medicinal products. In this case, the safety 
profile has not been validated by means of a marketing authorisation application, and no post-marketing 
monitoring has begun. Hence, thorough adverse event management is essential, above all to safeguard the 
safety of patients and, secondly, to ensure a fit-for-purpose evidence for any future marketing authorisation 
application. 

17 
 
 
 
Exposure will be lowest in the development phase and will in most instances increase significantly once the 
product receives marketing authorisation. In the first two years following market placement in the EU, the 
medicinal product is subject to additional monitoring. The additional monitoring may be extended, reflecting 
the need for further evidence, and hence is important to consider when evaluating the product's exposure 
and evidence base for setting the necessary risk level of adverse event management. 
 
 
Figure 4 Evidence base for safety data 
 

18 
 
 
 
 
7. Change log 
Changes from version 1.0 to 2.0: 
 
•
Section 2.2: New wording concerning additional 
monitoring list in the EU. 
•
Section 2.4: Clarification and new wording concerning 
trials with high mortality and establishing DSMB. 
•
Section 2.5: Clarification of which events must be included 
in ASR. 
•
Editorial changes throughout the document, including 
changes to the layout. 
Version 2.0 includes the 
following updates: 

Patientforberedelse til PET-, PET/CT-..., version 6. 
Udskrevet: 24-02-2025 af Marie Manon Krarup Stolberg 
1 af 10 
 
 
 
Patientforberedelse til PET-, PET/CT- og PET/MR-scanninger på Rigshospitalet 
Udgiver 
Rigshospitalet 
Dokumenttype 
Vejledning 
Version 
6 
Forfattere 
sektionsleder PET-scannersektion, overlæger PET- 
scannersektion 
Gældende fra 
12-12-2024 
Fagligt ansvarlig 
Annika Loft Jakobsen 
Næste revision 
12-12-2027 
Ændringer 
Dokument flyttet til Rigshospitalet og publiceret til alle. 
Ingen ændringer i indhold. 
 
Formål 
Målgrupper og anvendelsesområde 
Definitioner 
Fremgangsmåde 
Ansvar og organisering 
Referencer, lovgivning og faglig evidens samt links hertil 
Bilag 
 
Genvej til indhold 
 Henvisning til undersøgelse 
 Indikationer og kontraindikationer til PET, CT, MR 
 Forberedelse til undersøgelse - generelt 
 Helkropsscanninger 
 Hjernescanninger 
 Hjertescanninger 
 PET/MR-scanninger 
 
 
Formål 
 Beskrive henvisende afdelings ansvar ifm. patientforberedelser til PET-, PET/CT- og PET/MR-scanning ved 
Afdeling for Klinisk Fysiologi & Nuklearmedicin, Rigshospitalet 
 Beskrive kontraindikationer for PET-, PET/CT og PET/MR-scanning 
 
 
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Målgrupper og anvendelsesområde 
Vejledningen gælder for personale på kliniske afdelinger, der henviser patienter til PET-scanning, PET/CT-scanning 
eller PET/MR-scanning ved Afdeling for Klinisk Fysiologi & Nuklearmedicin, Rigshospitalet. 
 
 
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Definitioner 
PET = Positron Emissions Tomografi 

Patientforberedelse til PET-, PET/CT-..., version 6. 
Udskrevet: 24-02-2025 af Marie Manon Krarup Stolberg 
2 af 10 
 
CT = Computed Tomography 
MR = Magnetisk Resonans 
 
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Fremgangsmåde 
Henvisning til undersøgelse 
 Henvisning sendes via RIS til Afdeling for Klinisk Fysiologi, Nuklearmedicin og PET. 
 Henvisende læge udfylder og underskriver MR-kontrolskema 
 CT-skema udfyldes og underskrives 
 Henvisende læge skal forud for henvisningen sikre sig patientens samtykke til at få undersøgelsen foretaget. 
 
 
 
 Alle henvisninger visiteres på Afdeling for Klinisk Fysiologi & Nuklearmedicin, inden undersøgelsen bookes. 
 Der udføres PET- og PET/CT-scanninger i afsnit 3982, 3985 og 4011 på Blegdamsvej og i afsnit ØB 2.sal på 
Rigshospitalet Glostrup. 
 Der udføres PET/MR-scanninger i afsnit 3982 på Blegdamsvej. 
 
 
Indikationer, kontraindikationer og relative kontraindikationer til PET, PET/CT og 
PET/MR 
 Indikation 
 Mangfoldige, er angivet i forberedelsesskemaerne ved hver undersøgelse. 
 
 
 
Kontraindikation 
 Relativ ved gravide og ammende. 
 Metalgenstande i patienten, der IKKE er MR-kompatible, er kontraindikation for MR-scanning. 
Anfør type og operations-år i MR-kontrolskema:. 
 Metalklips i hjernen 
 Pacemaker (bemærk, at der kan sidde metal tilbage, selvom pacemakeren er fjernet) 
 Stent 
 Indopererede hjælpemidler som fx øreimplantat og insulinpumpe 
 Kunstige lukkemuskler 
 Elektroniske stimulatorer 
 Metalsplinter i øjne/krop: Angiv splintens art. 
 
 
 
Relative kontraindikationer 
 Graviditet: 
 Der foretages sædvanligvis ikke undersøgelser med ioniserende stråling på gravide kvinder. I 
sjældne tilfælde kan det dog være indiceret, og i så fald bør undersøgelsen konfereres med 
vagthavende læge på Afdeling for Klinisk Fysiologi, Nuklearmedicin og PET, tlf. 5-1379,mhp. at 
planlægge en skanning med lille dosis sporstof og ultra lavdosis CT. 
 Stort abdominalomfang: 
 Da PET/MR-scannerens åbning er forholdsvis lille (60 cm), kan patienter med meget stort 
abdominalomfang ikke være i scanneren. Lejet i scanneren har også en maksimal bæreevne. Mål 
patientens livvidde og kontakt PET-bagvagt på tlf. 5-1379, hvis der er tvivl om, hvorvidt patienten 
kan være i scanneren. 
 Motorisk uro og/eller manglende evne til at kooperere til undersøgelsen: 
 Hvis patienten ikke kan ligge helt stille under undersøgelsen, kan scanningen blive præget så meget 

Patientforberedelse til PET-, PET/CT-..., version 6. 
Udskrevet: 24-02-2025 af Marie Manon Krarup Stolberg 
3 af 10 
 
af uro, at den ikke kan tolkes. Sedering kan være en mulighed. 
 Fysisk tilstand: 

Patientforberedelse til PET-, PET/CT-..., version 6. 
Udskrevet: 24-02-2025 af Marie Manon Krarup Stolberg 
4 af 10 
 
 Ved fx smerter, rygproblemer eller gangproblemer må det overvejes om patienten kan ligge helt 
fladt på lejet i længere tid (>30min) under scanning. Hvis ikke dette er muligt, kan PET/MR- 
scanning vanskeligt gennemføres, og der anbefales separat PET/CT- og MR-scanning. 
 Klaustrofobi: 
 PET/MR-scanning frarådes til hjerne-demens-undersøgelser ved klaustrofobi, og separat PET/CT og 
MR skanning anbefales. Ellers skal tages stilling til evt beroligende medicin. 
 Da PET/MR-scannerens åbning er forholdsvis lille (60 cm) kan det for personer med svær 
klaustrofobi være svært at gennemføre undersøgelsen. Personalet i afdelingen har mulighed for at 
give patienten beroligende medicin forud for undersøgelsen 
 Da PET/CT-scannerens åbning er forholdsvis stor, vil de fleste, der blot lider af 
lettere klaustrofobi, kunne medvirke til en scanning. Personalet i afdelingen har mulighed for at give 
patienten beroligende medicin forud for undersøgelsen. 
 
 
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Forberedelse til undersøgelser - generelt 
Henvisende afdeling skal før undersøgelsen vurdere patienten med henblik på...: 
 
Ledsagende plejepersonale. Hvis patienten har brug for observation og pleje i undersøgelsesperioden, skal der 
være ledsagende personale med fra den henvisende afdeling. Personalet skal være uddannet i og i stand til at yde 
den pleje og/eller behandling patienten har behov for, herunder at kunne behandle forventelige komplikationer. 
Svar på plasma-kreatinin. Hvis der i forberedelsesskemaet er krav om ny plasma-kreatinin, påhviler det 
henvisende afdeling at sikre rettidig blodprøvetagning, og at svaret er tilgængeligt, inden PET/CT- eller 
PET/MR-scanningen skal foretages. Plasma-kreatinin svar anvendes i forbindelse med injektion af kontrast. 
Smertepalliering. Hvis patienten er plaget af smerter, er det henvisende afdelings ansvar, at denne er 
smertepallieret før scanningen. Det er vigtigt for resultatet af undersøgelsen, at patienten kan ligge stille i 
scanneren. 
Tolk. Hvis patienten ikke kan forstå nok dansk til at kooperere ved undersøgelsen, påhviler det henvisende 
afdeling af sørge for tolkning. 
Påklædning. Patienten skal være iført tøj uden metalknapper/lynlås mv. eller smykker svarende til det område, 
der skal scannes. Send gerne patientens strømper og sko med, da patienten skal ud at gå på gulvet. 
Injektion på sengeafdelingen. Patienter på intensive afsnit eller i isolation kan evt. få foretaget injektionen af 
det radioaktive lægemiddel på sengeafdelingen og transporteres til scanning til aftalt tidspunkt. Kontakt PET- 
bagvagt tlf.; 5-1379 for at planlægge forløbet. 
Transport. Det er henvisende afdelings ansvar at bestille transport til undersøgelsen. Afdeling for Klinisk 
Fysiologi, Nuklearmedicin og PET bestiller returtransport. 
 
 
 
 
 
Forløbet af undersøgelsen 
Patienten får injektion af et radioaktivt lægemiddel i en vene og hviler inden scanningen. Hviletiden varierer fra 5-60 
minutter. Patienten placeres på et leje, og den kropsdel, som skal undersøges, placeres i scannerens åbning. Ved 
scanning af hele kroppen kører lejet ind gennem scanneren. Scanningen opsamler data, hvorefter vi kan rekonstruere 
serier af billeder. 
Det kan tage lidt tid at blive placeret rigtigt i scanneren før undersøgelsens start. 
PET eller PET/CT-scanningen tager 15-45 minutter og giver ingen smerter eller anden form for ubehag. 
Ved tvivlsspørgsmål kan vagthavende læge på Afdeling for Klinisk Fysiologi & Nuklearmedicin 
kontaktes: 
PET-bagvagt tlf.: 5-1379. 
Drejer det sig om PET-hjerneundersøgelser, kontakt PET–hjerne-bagvagt tlf.: 5-7254 
Drejer det sig om PET-hjerteundersøgelser, kontakt KF–bagvagt tlf.: 5-1674 

Patientforberedelse til PET-, PET/CT-..., version 6. 
Udskrevet: 24-02-2025 af Marie Manon Krarup Stolberg 
5 af 10 
 
Ved PET/MR-scanning påspændes sædvanligvis antenner (coils) på det område, der skal skannes. 
PET/MR-scanning tager op til 1 time. Da PET/MR-scanneren larmer meget, får patienten høreværn på, og patient og 
scannerpersonale kommunikerer via et samtaleanlæg. 
Kontrast til CT eller MR: Intravenøs kontrast gives ved indsprøjtning i en vene. Kontrasten er uskadelig for kroppen og 
giver generelt ikke ubehag, dog eventuelt lette, forbigående bivirkninger i form af varme- og vandladningsfornemmelse 
samt metalsmag i munden. 
Drikkekontrast gives til visse undersøgelser 
Det er vigtigt, at patienten drikker rigeligt væske før og efter undersøgelsen. Dette medvirker til udskillelsen af det 
radioaktive lægemiddel og den intravenøse røntgenkontrast. Udskillelsen sker via urinen. 
Hvis patienten skal have væske via sonde eller intravenøst, kontakt PET-bagvagt tlf. 5-1379. 
 
 
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Patientforberedelser ved PET- og PET/CT-helkropsscanninger 
 
 
18F-FDG-PET-scanning el. 
18F-FDG-PET/CT-scanning 
Forberedelse 
Forberedelse, 
diabetespatienter 
Forberedelse ved 
visitation 
til CT med 
kontrast 
Indikationer: 
En lang række cancersygdomme: 
Diagnostik, stadieinddeling, 
responsmonitorering, 
recidivpåvisning og planlægning af 
stråleterapi. 
Påvisning af infektionsfoci og 
aktivitet i inflammatorisk sygdom. 
Faste 4 timer før 
undersøgelsen. Patienten må 
dog gerne drikke vand. 
Glukosedrop og parenteral 
ernæring skal være seponeret 
i 4 timer før undersøgelsen. 
Patienten bør undgå fysisk 
anstrengelse på 
undersøgelsesdagen 
Faste 4 timer før 
undersøgelsen. Patienten må 
dog gerne drikke vand 
Tage vanlige dosis insulin, før 
faste. Ekstra insulin må ikke 
tages i fasteperioden. 
Bruger patienten 
insulinpumpe, fortsættes med 
basalinsulin under faste. 
Pausere 48 timer med 
medicin, der indeholder 
Metformin, idet Metformin 
påvirker optagelsen af FDG i 
tarmen. 
Plasma-kreatinin 
eller GFR-værdi 
skal inden 
undersøgelsen 
være.: 
Ambulante 
patienter: Under 3 
måneder gammel 
Indlagte patienter: 
Under 7 dage 
gammel 
Akutte patienter: 
Under 24 timer 
gammel 
 
 
 
68Ga-DOTATOC-PET/CT- 
scanning el. 
64Cu-DOTATATE-PET/CT- 
scanning 
Forberedelse 
Forberedelse, 
diabetespatienter 
Forberedelse ved 
visitation til CT 
med kontrast 
Indikationer: 
Neuroendokrine tumorer (NET), 
påvisning og stadieinddeling 
Påvisning af fæokromocytom, 
neuroblastom, ganglioneurom og 
Ingen 
Ingen 
Plasma-kreatinin 
eller GFR-værdi 
skal inden 
undersøgelsen af 
være.: 
Ambulante 

Patientforberedelse til PET-, PET/CT-..., version 6. 
Udskrevet: 24-02-2025 af Marie Manon Krarup Stolberg 
6 af 10 
 
paragangliom 
Led i udredning af medullært 
thyroideakarcinom 
Vurdering af kendte tumores 
egnethed for radionuklidbehandling 
 
patienter: Under 3 
måneder gammel 
Indlagte patienter: 
Under 7 dage 
gammel 
Vurdering af 
progression/regression af 
ovennævnte tumorer 
Akutte patienter: 
Under 24 timer 
gammel 
 
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Patientforberedelse ved PET og PET/CT–hjernescanninger 
 
 
18F-FDG PET/CT- 
hjernescanning 
Forberedelse 
Forberedelse, 
diabetespatienter 
CT med kontrast 
Indikationer: 
Ikke-maligne sygdomme: 
Epilepsi. Præoperativ vurdering 
mhp. lokalisering af focus. 
Neurodegenerativ sygdom, tidlig 
diagnose og udbredelse, 
differential- diagnostisk 
subklassifikation, moni-torering af 
sygdomsudvikling. 
Faste 4 timer før 
undersøgelsen. Patienten må 
dog gerne drikke vand. 
Glukosedrop og parenteral 
ernæring skal være seponeret 
i 4 timer før undersøgelsen. 
Faste 4 timer før 
undersøgelsen. Patienten må 
dog gerne drikke vand. 
Patienten skal tage sin 
sædvanlige dosis insulin før 
faste. Ekstra insulin må ikke 
tages i fasteperioden. 
Bruger patienten 
insulinpumpe, fortsættes med 
basalinsulin under faste. 
Der benyttes ikke 
CT-kontrast ved 
denne 
undersøgelse 
Cerebrovaskulær sygdom. 
Inflammatoriske CNS-sygdomme: 
SLE, Sarkoidose, limbisk 
encephalitis. 
Maligne sygdomme: 
Primært CNS-lymfom 
 
 
 
18F-FET PET-hjernescanning 
Forberedelse 
Forberedelse, 
diabetespatienter 
CT med kontrast 
Indikationer: 
Vurdering af en uafklaret proces i 
hjernen. 
Præoperativ afgrænsning af et 
mistænkt gliom 
Postoperativ afgrænsning af 
resttumorvæv fra gliom 
Vurdering af en tumors 
malignitetsgrad 
Faste 4 timer før 
undersøgelsen. 
Patienten må dog gerne 
drikke vand. 
Der må i denne periode ikke 
gives parenteral ernæring, 
inkl. 
proteinholdig/aminosyreholdig 
ernæring. 
Faste 4 timer. 
Hvis det ikke er muligt at faste 
4 timer, må henvisende 
afdeling vurdere, hvilke 
forholdsregler omkring faste 
og diabetesmedicin der klinisk 
er muligt. Dog skal 
proteinholdig/aminosyreholdig 
ernæring i videst muligt 
omfang undgås 
Der benyttes 
vanligvis ikke CT- 
kontrast ved denne 
undersøgelse. Hos 
patienter med 
pacemaker eller 
anden 
kontraindikation for 
MR, kan der 
udføres CT før og 
efter kontrast, hvis 
det præciseres i 

Patientforberedelse til PET-, PET/CT-..., version 6. 
Udskrevet: 24-02-2025 af Marie Manon Krarup Stolberg 
7 af 10 
 
Mistanke om malign degeneration 
Planlægning af hjernebiopsi mhp. 
optimering af den diagnostiske 
kvalitet 
Differentialdiagnosticering mellem 
recidivtumor og strålefølger. 
Monitorering af 
behandlingsrespons – tidlig 
identifikation af tumorrecidiv. 
Vurdering af cerebrale metastaser 
indtegning af 
hjernetumorer/metastaser ved 
stråleterapiplanlægning. 
OBS: 18F-FET indeholder små 
mængder ethanol svarende til 1/8 
genstand (<1,5 g) som kan give 
lette reaktioner hos patienter i 
Disulfiram- (Antabus) eller 
metronidazol-behandling. Kontakt 
vagthavende ved spørgsmål, tlf. 
35457254. 
henvisningen. 
 
 
 
18F-FE-PE2I PET-hjernescanning 
Forberedelse 
Forberedelse, 
diabetespatienter 
CT med kontrast 
Indikationer 
Patienter med klinisk usikker 
Parkinsonisme 
Ingen 
Ingen 
Der benyttes ikke 
CT-kontrast ved 
denne 
undersøgelse 
OBS: 18F-FE-PE2I indeholder små 
mængder ethanol svarende til 1/8 
genstand (<1,5 g) som kan give 
lette reaktioner hos patienter i 
Disulfiram- (Antabus) eller 
metronidazol-behandling. Kontakt 
vagthavende ved spørgsmål, tlf. 
35457254. 
 
 
 
11C-PiB PET-hjernescanning 
Forberedelse 
Forberedelse, 
diabetespatienter 
CT med kontrast 
Indikationer: 
Mistanke om tilstande med øget 
amyloidophobning i hjernen. 
OBS: 11C-PiB indeholder små 
mængder ethanol svarende til 1/8 
genstand (<1,5 g) som kan give 
Ingen 
Ingen 
Der benyttes ikke 
CT-kontrast ved 
denne 
undersøgelse 

Patientforberedelse til PET-, PET/CT-..., version 6. 
Udskrevet: 24-02-2025 af Marie Manon Krarup Stolberg 
8 af 10 
 
 
lette reaktioner hos patienter i 
Disulfiram- (Antabus) eller 
metronidazol-behandling. Kontakt 
vagthavende ved spørgsmål, tlf. 
35457254. 
 
 
 
68Ga-DOTATOC-hjernescanning 
Forberedelse 
Forberedelse, 
diabetespatienter 
CT med kontrast 
Indikationer: 
Påvisning af aktivt meningeomvæv 
ved primærdiagnostisk, vurdering 
Ingen 
Ingen 
Der benyttes ikke 
CT-kontrast ved 
denne 
undersøgelse 
af resttumorvæv, mistanke om 
recidiv og stråleterapiplanlægning. 
 
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Patientforberedelser ved PET- og PET/CT-hjertescanninger 
 
 
82Rubidium PET/CT-hjertescanning 
Forberedelse 
Forberedelse, 
diabetespatienter 
CT med kontrast 
Indikationer: 
Vurdere tilstedeværelsen af 
iskæmigivende koronararteriesygdom 
hos patienter med intermediær 
prætest sandsynlighed for iskæmisk 
hjerte-sygdom. 
Fra kl. 16 dagen inden 
undersøgelsen må patienten 
ikke indtage koffein i form af 
fx chokolade, kaffe, cola, te 
eller energidrik 
Samme som for ikke- 
diabetespatienter 
Der benyttes ikke 
CT-kontrast ved 
denne 
undersøgelse 
Vurdere graden af iskæmi før 
stillingtagen til revaskularisering hos 
patienter med kendt 
koronararteriesygdom. 
Forud for undersøgelsen 
pauseres med følgende 
medicin: 
Mistanke om stum iskæmi. 
72 timer (4 dage): Viagra, 
Cialis, Levitra 
Før større operativt indgreb (fx nyre- 
transplantation) hos patienter med 
betydelig øget risiko for koronarsyg- 
dom. 
Kontrol efter hjertetransplantation. 
Kvantificering af koronar flowreserve 
48 timer (2 dage): 
Persantin, Asasantin 
24 timer (1 dag): Nuelin 
Retard, Teofylamin, Theo- 
dur, UniXan. 
12 timer: Cardopax, Fem- 
Mono Retard, Imdur, Isodur. 
2 timer: Discotrine-plaster, 
tages af senest to timer før. 
 
 
 
18F-FDG- PET/CT-hjertescanning 
Forberedelse 
Forberedelse, 
diabetespatienter 
CT med kontrast 
Indikationer: 
Faste 4 timer forud for 
undersøgelsen. Patienten må 
Ikke-insulinkrævende 
diabetes: Tage 
Der benyttes ikke 
CT-kontrast ved 

Patientforberedelse til PET-, PET/CT-..., version 6. 
Udskrevet: 24-02-2025 af Marie Manon Krarup Stolberg 
9 af 10 
 
Hjerteinsufficiens og svær 
koronarsygdom, hvor 
revaskularisering overvejes for at 
forbedre hjertets pumpefunktion. 
CTO (Chronic Total Occlusion) i 
koronararterie, forud for PCI- 
behandling. 
dog gerne drikke vand. 
diabetesmedicin som vanligt. 
Faste 4 timer forud for 
undersøgelsen. Patienten må 
dog gerne drikke vand. 
Insulinkrævende diabetes: 
Patienten må spise 
morgenmad og få sin insulin 
som vanligt. 
Insulin via pumpe: Faste 
4 timer forud for 
undersøgelsen og forblive 
tilkoblet insulinpumpe med 
vanlig basisinsulin. Patienten 
må dog gerne drikke vand. 
denne 
undersøgelse 
 
 
 
Kombineret 82Rubidium- og 
18F-FDG-PET-hjertescanning 
Forberedelse 
Forberedelse, 
diabetespatienter 
CT med kontrast 
Indikationer: 
Patienten skal forberedes til 
Patienten skal forberedes til 
Der benyttes ikke 
CT-kontrast ved 
denne 
undersøgelse 
begge undersøgelser. 
begge undersøgelser. 
Samme som for 82Rubidium 
Se "Forberedelse" i 
Se "Forberedelse, 
PET/CT–hjertescanning og 18F- 
ovenstående skemaer: 
diabetespatienter" i 
FDG- PET/CT – hjertescanning 
82Rubidium PET/CT– 
ovenstående skemaer: 
hjertescanning og 18F-FDG- 
82Rubidium PET/CT– 
PET/CT – hjertescanning 
hjertescanning og 18F-FDG- 
PET/CT – hjertescanning 
 
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Patientforberedelse ved PET/MR-scanninger 
 
 
18F-FDG PET/MR- 
hjernescanning 
Forberedelse 
Forberedelse, 
diabetespatienter 
MR med kontrast 
Indikationer: 
Ikke-maligne sygdomme: 
Faste 4 timer 
før undersøgelsen. Patienten 
må dog gerne drikke vand. 
Faste 4 timer før 
undersøgelsen. Patienten må 
dog gerne drikke vand. 
Der benyttes ikke 
MR-kontrast ved 
denne undersøgelse 
Neurodegenerativ sygdom, tidlig 
diagnose og udbredelse, 
differential- diagnostisk 
subklassifikation, monitorering af 
sygdomsudvikling 
Patienten skal tage sin 
sædvanlige dosis insulin før 
faste. Ekstra insulin må ikke 
tages i fasteperioden. 
Bruger patienten 
insulinpumpe, fortsættes med 
basalinsulin under faste. 
 
 
 
18F-FET PET/MR- 
hjernescanning 
Forberedelse 
Forberedelse, 
diabetespatienter 
Forberedelse ved 
visitation til MR med 

Patientforberedelse til PET-, PET/CT-..., version 6. 
Udskrevet: 24-02-2025 af Marie Manon Krarup Stolberg 
10 af 10 
 
 
kontrast 
Indikationer: 
Vurdering af en uafklaret proces i 
hjernen. 
Præoperativ afgrænsning af en 
mistænkt primær hjernetumor. 
Postoperativ afgrænsning af 
resttumorvæv fra primær 
hjernetumor. 
Vurdering af en tumors 
malignitetsgrad. 
Mistanke om malign degeneration. 
Planlægning af hjernebiopsi mhp. 
optimering af den diagnostiske 
kvalitet. 
Differentialdiagnosticering mellem 
recidivtumor og strålefølger. 
Monitorering af 
behandlingsrespons – tidlig 
identifikation af tumorrecidiv. 
Vurdering af cerebrale metastaser 
OBS. 18F-FET indeholder små 
mængder ethanol svarende til 1/8 
genstand (<1,5 g) som kan give 
lette reaktioner hos patienter i 
Disulfiram- (Antabus) eller 
metronidazol-behandling. Kontakt 
vagthavende ved spørgsmål, tlf. 
35457254. 
Faste 4 timer før 
undersøgelsen. 
Patienten må dog gerne drikke 
vand. 
Der må i denne periode ikke 
gives parenteral ernæring, inkl 
proteinholdig/aminosyreholdig 
ernæring. 
Faste 4 timer. 
Hvis det ikke er muligt at 
faste 4 timer, må henvisende 
afdeling vurdere, hvilke 
forholdsregler omkring faste 
og diabetesmedicin der 
klinisk er muligt. 
Dog skal protein- 
/aminosyreholdig ernæring i 
videst muligt omfang undgås. 
eGFR alternativt P- 
kreatinin skal foreligge 
inden scan- opstart 
hvis... 
Patienten har 
nedsat 
nyrefunktion. 
eGFR 
alternativt P- 
kreatinin må 
ikke være ældre 
end 30 dage. 
Hvis eGFR 
alternativ. P- 
kreatinin er ældre end 
30 dage, måler 
scannerpersonalet på 
Klinisk fysiologi & 
Nuklearmedicin, eGFR 
alternativt P- kreatinin. 
 
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Ansvar og organisering 
Ansvar hos henvisende afdelingers personale: Se afsnit "Fremgangsmåde" 
 
 
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Referencer, lovgivning og faglig evidens samt links hertil 
 Lov nr. 23 af 15/01/2018 om ioniserende stråling og strålebeskyttelse (findes på Retsinformation.dk) 
 Bekendtgørelse 669 af 01/07/2019 om ioniserende stråling og strålebeskyttelse §16, §61 (findes på 
Retsinformation.dk) 
 
Link til patientvejledninger på Rigshospitalets hjemmeside: 
 
Patientvejledninger til PET-undersøgelser findes på Rigshospitalets 
hjemmeside: https://www.rigshospitalet.dk/afdelinger-og-klinikker/diagnostisk/klinisk-fysiologi-og- 
nuklearmedicin/patientinformation/undersoegelse-paa-afdelingen/Sider/default.aspx 
 
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Patientforberedelse til PET-, PET/CT-..., version 6. 
Udskrevet: 24-02-2025 af Marie Manon Krarup Stolberg 
11 af 10 
 
Bilag 
Ikke relevant. 
 
 
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06.2.HEH.11.1.1.18F-FDG PET/CT generel, version 9. 
Udskrevet: 17-02-2025 af Anonymous 
1 af 7 
 
 
 
06.2.HEH.11.1.1.18F-FDG PET/CT generel 
Udgiver 
Herlev og Gentofte Hospital > Nuklearmedicin 
Dokumenttype 
Instruks 
Version 
9 
Forfattere 
Lene Skads 
Jeppson/LENJEP01/RegionHovedstaden, Nina 
Tietgen/NINTI/RegionHovedstaden 
Gældende fra 
07-05-2024 
Fagligt ansvarlig 
Helle W Hendel 
Næste revision 09-10-2024 
Ændringer 
Ændringer til afsnittet 'Forberedelse' - ændret fra gammel til ny version 
 
 
Formål 
Målgrupper og anvendelsesområde 
Undersøgelsesprincip 
Indikationer 
Kontraindikationer 
Graviditet og amning 
Forberedelse 
Definitioner 
Fremgangsmåde 
Fejlkilder 
Lægemidler, aktivitetsmængde og stråledosis 
Fortolkning og svar 
Ansvar og organisering 
Formularer 
Referencer, lovgivning og faglig evidens samt links hertil 
Bilag 
 
 
Formål 
Præcis anatomisk påvisning af foci med øget optagelse af glucoseanalogen fluordeoxyglucose (FDG). 
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Målgrupper og anvendelsesområde 
Sygeplejersker, bioanalytikere, radiografer og læger på Afdeling for Nuklearmedicin, som arbejder 
med PET/CT. 
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06.2.HEH.11.1.1.18F-FDG PET/CT generel, version 9. 
Udskrevet: 17-02-2025 af Anonymous 
2 af 7 
 
Undersøgelsesprincip 
18F-Fluordeoxyglucose (18F-FDG) er en radioaktivt mærket glukose analog, der anvendes som 
sporstof til at påvise celler med højt glukoseforbrug. Maligne og visse inflammatoriske celler har et 
højere stofskifte end normalt væv og øget optagelse af glukose og FDG. PET-skanning (positron 
emissions tomografi) kan man påvise FDG-fordelingen i kroppen og dermed identificere områder med 
tumorer, metastaser, infektioner og inflammation. 
Ved samtidigt at udføre (diagnostisk) CT-skanning kan den præcise lokalisation af FDG-optagelsen 
lokaliseres, hvilket øger den diagnostiske sikkerhed (specificiteten). Omvendt kan patologiske 
forandringer på CT-skanningen verificeres eller afkræftes. I flere tilfælde kan PET og CT visualiserer 
patologiske forandringer uafhængigt af hinanden; f.eks. kan PET ikke visualisere små lungemetastaser, 
og CT er i mange tilfælde mindre sensitivt til diagnosticering af knoglemetastaser. 
Der suppleres ofte med intravenøs røntgenkontrast En lav dosis CT-skanning (ldCT) udføres til 
attenuationskorrektion af PET-data og antomisk vejledning, hvis der ikke er brug for en diagnostisk 
CT skanning (f.eks. hvis patienten har en relativt ny CT-skanning) 
VARIGHED: 
2,5 – 3 timer (forberedelse, skanning, evt. ventetid) 
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Indikationer 
1. Onkologiske sygdomme mhp. primær diagnostik (ukendt primær tumor, c. occulta) og 
stadieinddeling samt som led i behandlingskontrol mhp. påvisning af restsygdom eller recidiv. 
Endvidere som led i planlægning af stråleterapi eller kirurgi, hvor det er afgørende præcist at 
kunne adskille vitalt tumorvæv fra ikke-vitalt væv. 
2. Infektionsudredning (alternativ til leukocytskintigrafi særligt ved kronisk/længerevarende 
infektion). 
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Kontraindikationer 
Ingen kontraindikation for PET-skanning, ud over svær adipositas (se specifikt for skanneren), eller 
tilfælde hvor patienten pga. svær klaustrofobi ikke vil være i skanneren, hvor besigtigelse af 
skanneren og evt. angstdæmpende medicin ikke skønnes effektfuldt. Ang. iv-kontrast, se ” Iodholdig 
kontraststof, Forholdsregler ved intravaskulær indgift”. 
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Graviditet og amning 
I tilfælde af graviditet må den henvisende læge sammen med en speciallæge fra PET-CT gruppen 
vurdere, om det er afgørende for patienten at få udført undersøgelsen. 
Normalt ingen ammepause. FDG udskilles ikke via mælken. For at mindske stråling fra mor (hjerne, 
hjerte, blære) til barn frarådes tæt kontakt de første 3-6 timer (3-5 halveringstider fra inj af tracer). 
Det anbefales at malke de første portioner mælk ud , så en anden kan give barnet mælken i en 
sutteflaske. 

06.2.HEH.11.1.1.18F-FDG PET/CT generel, version 9. 
Udskrevet: 17-02-2025 af Anonymous 
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Forberedelse 
Alle patienter skal faste i minimum 4 timer forud for undersøgelsen (injektion af sporstof). Patienten 
opfordres dog til at drikke vand i fasteperioden. 
Parenteral ernæring og/eller intravenøse væsker, som indeholder glucose (inkl GIK-drop), dextrose 
eller laktose, skal seponeres minimum 4 timer før FDG-injektionen. 
 
Hård motion indtil 24 timer før undersøgelsen skal undgås. 
For patienter, hvor der er klinisk mistanke om nedsat nyrefunktion eller har kendt nyresygdom, skal 
der foreligge eGFR der er mindre end 3 mdr gammel. 
Hos alle patienter med akut sygdom/indlagte skal der foreligge eGFR som er mindre end 7 dage 
gammel. 
 
Nedenfor beskrives hvordan patienter med diabetes skal forholde sig. 
I tvivlstilfælde kontaktes udgående diabetesteam (38681309). 
Patienter i behandling med Metformin og Metforminkombinationspræparater anbefales at pausere i 48 
timer før undersøgelsen. 
Type 2 patienter, som ikke får insulin: 
Antidiabetika skal tages som vanligt, fraset Metformin og Metforminkombinationspræparater som 
ovenfor anført. 
Faste 4 timer før tracer-injektion. 
Insulinkrævende diabetespatienter (både type 2 og type 1): 
Indtagelse af morgenmad og morgen-insulin (dette gælder både basalinsulin og bolusinsulin) mindst 4 
timer før injektion af sporstof. Faste 4 timer før injektion af sporstof. Ingen insulin-injektioner i 
fasteperioden. 
Insulinpumpepatienter (type 1 diabetes): 
Faste 4 timer før injektion af sporstof. Ingen insulin-bolus i fasteperioden. Pumpen skal uændret 
afgive basalinsulin i fasteperioden. 
Hos patienter med insulinkrævende diabetes (injektionsbehandling og insulinpumpebærere) og hvis 
blodsukker > 10 mmol/l, kan gives hurtigtvirkende insulin Novorapid efter sliding scale indtil 4 timer 
før injektion af sporstof. Skal patienten undersøges kl. 11, skal der således måles blodsukker ved 6- 
tiden for at kunne nå at administrere Novorapid.. 
Blodsukkermåling gentages efter tre timer. Måles der fortsat blodsukker > 10 mmol/l kontaktes 
Afdeling for Nuklearmedicin mhp. om undersøgelsen skal aflyses/rykkes. 
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Definitioner 
Ikke relevant. 

06.2.HEH.11.1.1.18F-FDG PET/CT generel, version 9. 
Udskrevet: 17-02-2025 af Anonymous 
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Fremgangsmåde 
Apparatur: 
Siemens Biograph mCT, Siemens Biograph mCT FLOW, samt Siemens Biograph Vision. 
Udførsel: 
Skanneren: 
Der udføres daglig kvalitetskontrol hver morgen, se vejledning. Henvisningen gennemgås mhp. 
forberedelse af patienten (anxiolytika, e-GFR og i.v. adgang). 
Hvileområde: 
Patienten identificeres ved navn og cpr.nr. På arbejdsskemaet noteres vægt, højde, samt for kvinder i 
den fertile alder (13-55 år) mulig graviditet. I tvivlstilfælde udføres graviditetstest. Patienten skal 
bekræfte, at faste er overholdt og spørges om diabetes. 
Hvis patienten er visiteret til i.v.-kontrast, udfyldes arbejdsarket ang. kontraindikationer (se: ” 
Iodholdig kontraststof, Forholdsregler ved intravaskulær indgift”). 
Patienten placeres på sengeleje i afslappet rygstilling. 
Angste patienter eller patienter med kendt tendens til muskelspændinger (f.eks. smertebetingede 
muskelspændinger) gives evt. tablet Diazepam 2 mg. per. os før injektion af 18F-FDG. 
Der anlægges venflon i armvene: 
 PET-CT med i.v. kontrast: venflon 18 G (grøn) 
 PET eller PET-CT uden i.v. kontrast 22 G (blå) 
På venflonen påsættes en membranprop (Luer Access Split-Septum) 
Hos alle patienter måles glukoseværdien før skylning af NaCl 0,9 % eller som beskrevet nedenfor og 
altid før injektion af 18F -FDG: 
 Fra venflon eller ved hjælp af microlet lancetter udtages blod til glukosemåling på Contour next 
glukoseapparat. 
 Resultatet noteres på arbejsskemaet. 
 Hvis glukoseværdien er > 8 mmol/l drøftes situationen med PET-afsnittets vagthavende læge 
(tlf. 8 1675) 
I.v. adgangen skylles igennem med NaCl 0,9% i 10 ml sprøjte. 
 
Når der er sikret fri passage, injiceres 18F –FDG afhængig af patientvægten. 4MBq 18F –FDG pr kg 
legemsvægt, minimum 150 MBq og maksimum 400 MBq via venflonen vha. Intego. For patienter med 
BMI ≥ 35 rådføres med PET-afsnittes vagthavende læge (tlf. 8 1675), om FDG-dosis skal øges til 4,5 
MBq/kg, minimum 400 MBp, max 500 MBp (se vejledning). 
Ved håndinjektion injiceres i trevejshane. Der skylles grundigt med NaCl 0,9% i begge studser. 
Klistermærke med sporstof, dosis, samt optrækstidspunkt sættes på arbejdsarket og 
injektionstidspunktet noteres herpå. 
Der dokumenteres for injektion i QDOC. Ved håndinjektion indskrives dosis manuelt. 

06.2.HEH.11.1.1.18F-FDG PET/CT generel, version 9. 
Udskrevet: 17-02-2025 af Anonymous 
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Patienten hviler herefter i ca. 45 minutter og lader derefter vandet. 
 Alt uønsket metal fjernes fra patienten inden undersøgelsen 
 Patientens cpr-nummer tjekkes på skærmen i skannerrummet 
 Patienten instrueres i at ligge uden at bevæge sig under hele undersøgelsen 
 Placér patienten centralt på lejet på ryggen med hoved hvilende i hoved-holderen. Brug evt. 
kiler til fiksation 
 Der gives evt. knæpude og armene lejres over hovedet, evt. på pude 
 Hvis patienten ikke kan have armene over hovedet, lægges armene ned langs siden og spændes 
fast med det brede bånd (husk at fjerne ur og ring) 
 Ved manuel injektion fjernes trevejshane inden skanning 
Den inderste lasers placering afhænger af protokollen. Der skannes i protokol 926, 927, 935-950, 960 
eller 961. Se protokoloversigt. 
PET/CT planlægning og optagelse: Se instrukserne for den pågældende skanner. 
Undersøgelsen planlægges således, at PET-skanningen opstartes 60 minutter ± 5 minutter efter 18F - 
FDG-injektion. Ved afsluttet undersøgelse dokumenteres i QDOC. For CT-skanningen indskrives 
kontraststof + dosis og evt. udfordringer/kontraindikationer. For PET-skanningen noteres evt. 
forsinkelser/generelle udfordringer med hele skanningen. 
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Fejlkilder 
 Kontaminering 
 Artefakter: Metal i kroppen (porta kath., plomber i tænder, proteser og andre 
stråleabsorberende genstande) 
 Dårlig lejring af patienten 
 Uro hos patienten i hvile-perioden 
 Uro hos patienten under optagelsen (bevægelsesartefakter) 
 Hård fysisk aktivitet 24 timer inden injektion 
 Højt insulinniveau, trods normalt blodsukker 
 Forsinket eller forlænget delay time (dvs. optagelsen er startet for tidligt/for sent) 
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Lægemidler, aktivitetsmængde og stråledosis 
Stråledosis til patienten skal søges at holdes så lav som muligt, under hensynstagen til opnåelse af 
brugbare billeder. 
Røntgendosis: Stråledosis ved helkropsskanning ~ 11,7 mSv, thorax/abdomen ~ 10 mSv. 
Ved ”lavdosis-CT 50mA” er stråledosis ca. 2,8 mSv. 
Effektiv dosis (18F -FDG): 8 mSv (±10 %) ved standard dosis på 370 MBq 18F -FDG 
LÆGEMIDDEL/DOSIS: 
PET-tracer: 
18F- Fluordeoxyglucose (FDG). 
4 MBq (±10 %) 18F–FDG pr kg legemsvægt, minimum 150 MBq og maksimum 400 MBq 

06.2.HEH.11.1.1.18F-FDG PET/CT generel, version 9. 
Udskrevet: 17-02-2025 af Anonymous 
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Patienter med BMI > 35, som tidligere har været skannet på standarddosis (4 MBq/kg), gives 500 
MBq 18F-FDG mhp. optimering af billedkvaliteten, hvis standarddosis har givet forringet 
billedkvalitet (konference med vagthavende læge) 
iv-kontrast: 
Omnipaque 350 mgI/ml, indgives efter vægt (se display på kontrastsprøjte) 
Muskelafslapning/sedering/angstdæmpning: 
Tbl. Diazepam 2 mg p.o. 
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Fortolkning og svar 
Der afgives skriftligt svar i RIS. 
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Ansvar og organisering 
Overbioanalytikeren har ansvaret for at indholdet i denne instruks er korrekt og fyldestgørende. Den 
enkelte medarbejder har ansvaret for at kende og følge denne vejledning. 
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Formularer 
Ikke relevant. 
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Referencer, lovgivning og faglig evidens samt links hertil 
LOV nr. 23 af 15/01/2018 
BEK 669 af 01/07/2019 
BEK 670 af 01/07/2019 
BEK 671 af 01/07/2019 
 
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Bilag 
Ikke relevant. 
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06.2.HEH.11.1.1.18F-FDG PET/CT generel, version 9. 
Udskrevet: 17-02-2025 af Anonymous 
7 af 7