Conditions: Prostate Cancer
Keywords: Prostate cancer PET/CT
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 239
Healthy volunteers: no

Brief summary:
The main purpose of this phase II trial study is to determine whether a positron emission tomography (PET)/computed tomography (CT) scan using 18F-DCFPyL affects the clinical management plan in Veterans.

In this study, the management plan prior to and after 18F-DCFPyL PET/CT will be recorded by specific questionnaires and corresponding changes in management will be analyzed. The scan will be used to see how the disease has spread. Both the treatment strategies and probable disease outcomes as relevant to clinical endpoints will be assessed. This study is open to Veterans only.

Detailed description:

Arms:
arm 1: Subjects receive a PET/CT scan.

Interventions: intervention 1: 18F-DCFPyL
Intervention descriptions: intervention 1: Study participants will receive intravenous administration of 18F-DCFPyL and undergo a PET/CT imaging study. Patients may be reenrolled in the study, if 18F-DCFPyL PET/CT is performed for subsequent management decision.

Protocol document:
Prot_SAP_000.pdf: 
 
 
P a g e 1 | 28  
  
 
Cover Page: 
 
 
 
 
 
Brief Title: 18F-DCFPyL PET/CT Impact on Treatment Strategies for Patients 
With Prostate Cancer 
 
 
 
NCT Number: NCT04390880 
 
 
 
Unique Protocol Id: 2019-099757 
 
 
 
 
 
 
Date: 08/22/2023 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
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Preliminary Results: 
PSMA-based 18F-DCFPyL PET/CT scan for Detection and Staging of Prostate 
Cancer in Comparison with Multiparametric MRI 
 
Introduction and Objective: F-[18]-labelled DCFPyL is a 2nd generation prostate-specific 
membrane antigen (PSMA)-based PET tracer. This study aimed to assess the efficacy of 18F-
DCFPyL PET/CT scan for detection of intra-prostatic and extra-prostatic lesions in individuals with 
clinically significant prostate cancer (PCa), compared to multiparametric MRI (mpMRI) of prostate.  
 
Methods: This IRB-approved, HIPAA-compliant, single-center, prospective study was nested in a 
clinical trial which assesses clinical applications of 18F-DCFPyL PET/CT in individuals with PCa. 
Data of 150 patients who had undergone 18F-DCFPyL PET/CT scan were reviewed and 41 patients 
(mean age 69, ranged 55-92 years, mean serum PSA 18.6 ng/mL at the time of performing scan) 
who had completed a diagnostic mpMRI no more than three months before acquisition of 18F-
DCFPyL PET/CT were included. PET/CT scans and mpMRIs were interpreted independently and 
findings were compared later. Positive mpMRI was defined as having PIRADS category 3-5 
lesion(s). The pre- and post- scan questionnaires were completed by the referring physician within 
two weeks before and four weeks after 18F-DCFPyL PET/CT study, respectively.  
 
Results: For localization of intraprostatic lesions, 18F-DCFPyL PET/CT scan and mpMRI were 
concordant in 78% (32/41) of the study cohort. The scans were discordant in 9 patients for this 
purpose, of whom two had negative, and one had non-diagnostic mpMRI. Positive regional and 
non-regional lymph nodes were found in 31.7% (13/41) and 7.3% (3/41) of individuals on 18F-
DCFPyL PET/CT, respectively, vs. regional pelvic lymph nodes in 2.4% (1/41) on mpMRI. Skeletal 
metastasis was detected in 17.1% (7/41) by 18F-DCFPyL PET/CT compared to 2.4% (1/41) by 
mpMRI. Overall, based on the results of 18F-DCFPyL PET/CT scan, staging was altered in 43.9% 
(18/41) of patients.  
 
Conclusion: 18F-DCFPyL PET/CT scan and mpMRI were concordant for localization of 
intraprostatic lesions in 78% of the study cohort. 18F-DCFPyL PET/CT is more sensitive to detect 
regional and non-regional lymph nodes and skeletal metastasis. Concurrent acquisition of 18F-
DCFPyL PET/CT and mpMRI can be beneficial for patient care in the diagnostic path of PCa. 
 


 
 
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1 Clinical Protocol  
1.1 IMPACT OF 18F-DCFPyL PET/CT ON INITIAL AND SUBSEQUENT TREATMENT 
STRATEGIES OF PATIENTS WITH PROSTATE CANCER (PROSPYL).  
1.1.1 BACKGROUND AND RATIONALE  
Prostate cancer is the most commonly diagnosed cancer and second leading cause of cancer 
death in American men (Edwards et al., 2014). Imaging and staging of prostate cancer is critical 
for treatment planning. Existing conventional imaging (CT, MRI and bone scans) has a low 
sensitivity in detecting local recurrence or metastatic disease. Choline based PET tracers are 
commonly used because of their affinity to prostate cancer but their diagnostic capability is limited, 
and they cannot reliably identify local recurrence, lymph node involvement, or soft-tissue deposits 
(Evangelista et al., 2013; Perera et al., 2016). Gallium-68 labeled HBED-CC PSMA (more 
commonly called 68Ga-PSMA-11) has been shown to be superior to choline based PET agents 
for the staging of prostate cancer, both Carbon11 and Fluorine-18 compounds (Afshar-Oromieh 
et al., 2014; Morigi et al., 2015; Schwenck et al., 2017). PSMA is expressed on the majority of 
prostate cancer cells, and is an ideal cell membrane protein to image. The detection rate of PSMA-
11 for metastatic lesions in patients with recurrent prostate cancer is high: 50% for patients with 
a PSA less than 1 ng/ml, and above 85% for patients with a PSA greater than 2 ng/ml (Eiber et 
al., 2015; Perera et al., 2016). Several studies have reported a high impact on management of 
patients with biochemical recurrence after curative primary treatment with a rate of management 
change of 61%, 53%, 62%, 76% (Albisinni et al., 2017; Hope et al., 2017; Roach et al., 2017; 
Sterzing et al., 2016). In two studies, the impact on management was lower for initial staging 
indication: 26% and 21% (Roach et al., 2017; Sterzing et al., 2016). Limitations of 68Ga-PSMA-
11 PET imaging include: a) rapid urinary excretion resulting in intense bladder accumulation 
obscuring the prostate region, 2) the requirement of local radionuclide generators for labeling 3) 
shorter half-life and reduced spatial resolution as compared to 18F agents. Recently developed 
second-generation PSMA PET probes using an 18F label, for example 18F-DCFPyL, overcome 
these limitations of 68Ga-based tracers. Preliminary studies have shown that 18F-DCFPyL to be 
promising for evaluation of metastatic prostate cancer. Therefore, we intend to perform a separate 
analysis of initial versus subsequent management as management options are considerably 
different (curative versus salvage/palliative). 
 
1.1.2 OBJECTIVE  
To determine the impact of 18F-DCFPyL PET/CT on initial and subsequent treatment strategies of 
patients with prostate cancer.  
  
1.1.3 STUDY SYNOPSIS  
This is a prospective, Phase II, open-label study in patients with prostate cancer. Study 
participants will receive intravenous administration of 18F-DCFPyL and undergo a PET/CT 
imaging study. Patients may be reenrolled in the study, if 18F-DCFPyL PET/CT is performed for 
subsequent management decision.  
1.1.3.1 Trial Size  
400 total patients  


 
 
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1.1.3.2 Study Schedule and Flow Chart  
  
Figure 1: Questionnaires timeline  
  
1.1.3.3 Endpoints Primary 
Endpoint:   
Intended and implemented management changes after 18F-DCFPyL PET/CT assessed separately 
for initial and subsequent treatment decisions.  
Secondary Endpoints:   
1. Prognostic value of the 18F-DCFPyL PET/CT miTNM classification (described below) for 
biochemical PFS, radiographic PFS and overall survival.  
2. Positive predictive value (PPV) on a per-patient and per-region basis (Table 1) of 18F-DCFPyL 
PET for detection of tumor location confirmed by histopathology/biopsy or follow-up assessed 
separately for initial staging and restaging.  
  
Region  
Description  
1  
Prostate Bed  
2  
Pelvic lymph nodes  
3  
Extrapelvic soft tissue, lymph nodes and visceral metastases   
4  
Bone metastases  
Table 1: Region Definition  
  
1.1.3.4 Study Timeline Primary 
Completion:  


 
 
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The study will reach primary completion 36 months from the time the study opens to accrual.  
Study Completion:  
The study will reach study completion 48 months from the time the study opens to accrual.  
  
1.1.4 INCLUSION EXCLUSION CRITERIA  
Inclusion criteria  
1. Patients who fulfill criteria for initial staging or restaging as outlined below:  
1) Initial treatment strategy decisions (initial staging)  
All patients with histologically proven prostate cancer or strong suspicion of prostate 
adenocarcinoma based on very high PSA levels (>50 ng/mL) who require an initial 
treatment/management decision who may be candidate for any of the following 
strategies:  
A) Surgery  
B) External radiation therapy (RT) C) Other focal therapies  
D) Systemic medical treatment E) 
Watchful waiting  
2) Assessment for Subsequent treatment strategy (restaging), any of the following:  
A) Patients with biochemical recurrence who are potential candidates for any salvage 
treatment. Biochemical recurrence is defined by rising PSA after definitive therapy 
with prostatectomy or radiation therapy, as any of the following:   
a. Post radical prostatectomy (RP): PSA equals to or greater than 0.2 ng/mL 
measured more than 6 weeks after RP  
b. Post-radiation therapy : Nadir + greater than or equal to 2 ng/mL rise in PSA  
B) Patients with known prostate cancer who undergo restaging because of new 
symptoms   
C) Patients with known metastatic prostate cancer who undergo restaging because of 
rising PSA with negative or inconclusive conventional imaging  
D) Patients with known prostate cancer who are treated medically or with RLT in whom 
response to treatment is assessed  
2. Capability to provide written informed consent  
3. Able to remain still for duration of each imaging procedure (about 30 minutes)   
  
* Patients may be reenrolled in the study, if 18F-DCFPyL PET/CT is performed for subsequent 
management decision.  
  
Exclusion criteria  
1. Less than 18 years-old at the time of radiotracer administration  
2. Inability to complete the needed investigational and standard-of-care imaging examinations 
due to other reasons (severe claustrophobia, radiation phobia, etc.)  
3. Any additional medical condition, serious concurrent illness, or other extenuating circumstance 
that, in the opinion of the Investigator, may significantly interfere with study compliance.  
4. Inability to provide written informed consent  


 
 
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1.1.5 ENROLLMENT PROCEDURES  
1.1.5.1 Patient screening:   
Laboratory values: all patients must have a recent serum PSA measurement (within 30 days prior 
to the 18F-DCFPyL)  
1.1.5.2 Informed Consent Process:  
All participants will be provided a consent form describing the study with sufficient information for 
participants to make an informed decision regarding their participation. Participants must sign the 
IRB approved informed consent prior to participation in any study specific procedure.  
  
1.1.6 IMAGING AGENT INFORMATION  
1.1.6.1 Study Agent:  
• 
18F-DCFPyL Injection is a sterile, clear particle-free solution supplied at a specific activity 
of at least 1000 mCi/μmol at the Time of Administration (TOA), and a radioactivity concentration 
(RAC) of 1-90 mCi/mL at the Time of Calibration (TOC). The TOC is at the end of synthesis 
(EOS). A dose of 9 ± 1 mCi (333 ±37 MBq) 18F-DCFPyL Injection will be administered via an in-
dwelling catheter placed in an antecubital vein or an equivalent venous access under the direct 
supervision of study personnel. The bolus will be injected at a rate of approximately 1ml/3-5 
seconds.  The maximum amount of injected active drug will be less than 4.02mcg. The injection 
will be followed by a 10-ml saline flush (sodium chloride IV infusion 0.9%) over approximately 10 
seconds. The pre-injection and post-injection syringe assay will be measured for total 
administered dose measurement. 18F-DCFPyL will be provided by Progenics pharmaceutical Inc. 
and sent directly to the VA GLA Healthcare System Imaging Service – Department of Nuclear 
Medicine. Drug will be stored per manufacturers’ recommendations in the Radio-isotope Lab until 
it is injected into the subject. A single dose will be ordered the day before study intervention and 
will be delivered by the afternoon of the day of study intervention by air and ground 
transportation. 
 
1.1.6.2 Characteristics of 18F-DCFPyL Injection: 
• 
Dosage Form: Sterile solution for intravenous injection 
• 
Appearance: Clear and free of visible particulate matter 
• 
pH: 4.5 – 7.5 
• 
Total Radioactivity (18F) per dose at TOA: 4.5 – 7.5 
• 
Radiochemical Purity: ≥95% 
• 
Specific Activity at TOA: ≥1000 mCi/μmol 
 
1.1.6.3 Storage and Handling: 
Following releasing the drug product by the cGMP-compliant PET production facility, each unit 
dose of 18F-DCFPyL Injection for intravenous injection should be stored at room temperature and 
administered by the labeled expiration time (10 hours from EOS). 18F-DCFPyL Injection must not 
be diluted. The drug product contains radioactive material and should only be handled by 


 
 
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personnel trained and experienced in the use of radioactive isotopes with proper shielding and 
monitoring. Receipt and use are limited to a facility licensed by the Federal or State office for 
Radioactive Substances. Unused or residual waste should be disposed of as radioactive waste 
following the institution’s standard operating procedures (SOPs) and/or applicable regulations or 
guidance. 
 
The study drug will be delivered by Progenics contract manufacturer, at ~9mCi dose syringe. It 
will be able to deliver the final drug product to the VA Greater Los Angeles, department of Nuclear 
Medicine.  
 
Toxicity will be attributed to specific study drugs based on judgment of the treating physician, or 
study PI or co-investigators. Toxicity will be judged as likely related, possibly related, or unlikely 
related to the study drug. If likely or possibly related, the next 18F-DCFPyL PET-CT imaging will 
be canceled. In the situation where an unexpected toxicity is observed but not clearly attributable 
to a study drug or procedure, then attempts will be made to identify the source of toxicity along 
with treatment and/or palliation of the toxicity.  
 
1.1.7 STUDY PROCEDURE AND IMAGING SPECIFICS  
1.1.7.1 Modality:  
PET/CT  
1.1.7.2 Study Procedures:  
Patient preparation  
1. No fasting is required.  
2. All patients will be screened by a VA Nuclear Medicine physician and then accepted for 
scanning if clinically appropriate.  
3. Informed consent will be obtained.  
Investigational drug administration:  
1. A dose of ~9mCi 18F-DCFPyL i.v. will be administered.   
2. Oral hydration and voiding is recommended immediately before start of the scan.   
Safety Monitoring  
1. Vital signs will be assessed before and after injection of 18F-DCFPyL (HR and supine BP).    
2. Patients will be monitored for adverse events during injection and for two hours after radiotracer 
administration.    
Imaging Specifics  
1. Whole-body (skull base to mid-thighs) PET/CT images will be obtained using the Siemens 
Biograph mCT or Vision scanners.  
2. PET/CT images will be acquired in 3D mode at 50-100 minutes after injection of ~9mCi of 18F-
DCFPyL.  


 
 
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3. Scan coverage will extend from mid-thigh to the base of the skull, starting from the mid-thighs 
to prevent urinary bladder radiotracer accumulation at the start of PET imaging.  In certain 
circumstances, coverage may be extended to the toes.  
4. A minimum of 3 minutes per bed position or equivalent will be used.  
5. Contrast may be administered if requested by the referring clinician and is decided site 
dependent.   
6. The PET emission scan is corrected using segmented attenuation data of the CT scan. PET 
images are reconstructed using ordered subset expectation maximization (OSEM) with 2 
iterations and 8 subsets.  
1.1.7.3 Analysis:  
1. PET/CT Images will be reviewed and analyzed using Siemens Syngo/TrueD workstation and 
Oasis workstation by a board-certified nuclear medicine physician experienced in reading 
PET/CT.   
2. A molecular imaging TNM (miTNM) framework for 18F-DCFPyL PET/CT prostate cancer 
staging will be used (described in 2.3.8 Analysis Specifics).  
  
1.1.8 ANALYSIS SPECIFICS  
1.1.8.1 Impact on Management Questionnaires to Referring Physicians  
A pre-scan questionnaire (Q1), a post-scan questionnaire (Q2) and a follow-up questionnaire (Q3) 
will be used to determine whether 18F-DCFPyL PET/CT affected intended patient management 
and whether these intended treatment strategies were finally implemented. Patients can only be 
enrolled in the study if the pre-PET questionnaire (Q1) is completed.  
  
The post-test questionnaire (Q2), has to be completed by the referring physician within 4 weeks 
after each 18F-DCFPyL PET/CT. The final third late follow-up questionnaire (Q3), has to be 
completed by the referring physician within 3 to 6 months after each 18F-DCFPyL PET/CT. 
Verification of management changes will also be done via chart review and telephone interview.  
  
Treatment Modalities and sub-modalities will be categorized as following for modality based 
analysis:   
A) Surgery  
a. Prostatectomy or Prostate Bed Surgery  
b. Pelvic Lymph Node dissection  
c. Solitary LN dissection  
d. Other  
B) External radiation therapy (RT)  
a. Prostate or Prostate Bed RT  
b. Pelvic lymph node RT  
c. Solitary LN Stereotactic body radiation therapy (SBRT)   
d. Lumbo-aortic RT (standard or SBRT)  
e. Oligo-metastasis SBRT C) Other focal therapies  
a. HIFU  
b. Brachytherapy  


 
 
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c. Cryotherapy  
d. Other  
D) Systemic medical treatment  
a. ADT  
b. Chemotherapy  
c. Immunotherapy E) Radionuclide therapy  
a. 
bone targeted radionuclide therapy  
b. 
PSMA targeted radionuclide therapy F) Watchful 
waiting  
  
Treatment management will also be categorized as follow for disease stage management based 
analysis:  
A) Local Prostate Fossa therapy  B) 
Regional Pelvic therapy  
C) Lombo-aortic LN focused therapy  
D) Solitary LN or oligometastatic disease focused therapy  
E) Metastatic disease systemic therapy  
  
1.1.8.2 Molecular Imaging TNM (miTNM) Framework  
18F-DCFPyL PET/CT provides unprecedented accuracy for whole body staging of prostate 
cancer. As 18F-DCFPyL PET/CT is increasingly adopted in clinical trials and routine practice 
worldwide, a unified language for image reporting is urgently needed. We anticipate worldwide 
adoption of PSMA PET/CT fueled by upcoming evidence and inclusion into guidelines. Thus, 
reporting standards must now be created to aid reproducible staging and restaging, enhance 
communication and ultimately support acceptance of this technology to the benefit of prostate 
cancer patients.  
  
Our group (UCLA) has made a proposal of a molecular imaging tumor, node and metastasis 
system (miTNM Version 1.0) as a standardized reporting framework for 18F-DCFPyL PET/CT or 
PET/MRI.  
  
miTNM organizes staging of whole-body prostate cancer by including information on exact 
location, pattern of disease distribution, PSMA expression and level of confidence. miTNM aims 
to aid information exchange by unifying clinical and research reporting of 18F-DCFPyL PET/CT. 
miTNM has to be prospectively evaluated to assess its impact on patient prognosis and 
management.  
  
The details of miTNM are provided below:  
  
A) PSMA expression score:  
PSMA expression categories are defined in relation to mean uptake in blood pool, liver and parotid 
gland. Results are reported 0, +, ++, +++ for no, low, intermediate or high level of PSMA 
expression, respectively, as outlined below (Table 2, Figure 2). Scores ++ and +++ are considered 
typical for prostate cancer lesions and favorable for PSMA-directed radioligand therapy.   


 
 
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Score  
PSMA expression  
Uptake  
0  
no  
Below bloodpool  
+  
low  
Equal to or above bloodpool and lower than liver  
++  
intermediate  
Equal to or above liver and lower than parotid gland  
+++  
high  
Equal to or above parotid gland  
Table 2: miPSMA expression score.  
  
  
  
Figure 2: PSMA expression score. Thresholds are demonstrated on a 18F-DCFPyL PET 
maximumintensity projection image. Note that bloodpool uptake is determined in the center of the aortic 
arch.  
  
B) Local tumor (T) (Table 3, Figure 3)  
miT2 to T4 categorize tumor extent with prostate in place, both treated or untreated. Local organ 
confined tumor is defined as miT2u for unifocal and miT2m for multifocal involvement. 
Extraprostatic extension is classified by three categories, in accordance with clinicopathologic 
TNM: Limited extraprostatic extension (miT3a); involvement of seminal vesicles (miT3b); 
infiltration of external sphincter, rectum, bladder, levator muscles, and/or pelvic wall (miT4).   
The presence of local recurrence in men after radical prostatectomy is categorized by miTr. 
Infiltration of pelvic structures should be detailed in the report.   
  
Local tumor (T)  
 miT0   
No local tumor  
 miT2  Organ confined tumor, report intraprostatic tumor location(s) on sextant base   u 
Unifocality   m Multifocality  
miT3  
 
Non-organ confined tumor, report intraprostatic tumor location(s) on sextant base 
  
a  Extracapsular extension   


 
 
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  miT4  b  
 
Tumor invades seminal vesicle(s)  
Tumor invades adjacent structures other than seminal vesicles, such as external 
sphincter, rectum, bladder, levator muscles, and/or pelvic wall.  
miTr  
 
Presence of local recurrence after radical prostatectomy  
Table 3: Molecular imaging T classification for PSMA PET/CT.  
  
  
Figure 3: miTNM categories and pattern of local tumor extent  
  
Anatomical distribution of intraprostatic tumor extension information of prostate involvement is 
described on sextant base. For sextant segmentation the craniocaudal extent of the prostate is 
divided into three volumes of equal thickness. Volumes will be separated into left and right of the 
urethra, so as to obtain left basal (LB), right basal (RB), left mid (LM), right mid (RM), left apical 
(LA), right apical (RA) segments (Table 4).  
  
Segment  
miT2-4 template  
LB  
Left base  
RB  
Right base  
LM  
Left mid  
RM  
Right mid  
LA  
Left apex  
RA  
Right apex   
Table 4: Sextant segmentation of prostate gland  
  
Probability of local tumor increases with focal uptake, higher PSMA expression score in the 
prostate other than the bladder neck/urethra area, higher PIRADS score, circumscribed CT 
contrast enhancement and/or signs of extra prostatic extension.  
  


 
 
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PSMA-positive pitfalls such as acute prostatitis and MRI-positive pitfalls such as post-biopsy 
changes and benign nodules have to be ruled out.  
  
C) Pelvic nodes (N)  
Pelvic nodal metastases will be categorized into single (miN1) and multiple (miN2) diseased lymph 
node regions (Table 5).   
  


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Regional nodes (N)  
 
  
miN0  
  
No positive regional lymph nodes  
 
  
miN1  
  
Single lymph node region harbors lymph node metastases,  
report location by a standardized template.  
 
miN2  
  
Multiple (≥2) lymph node regions harbor lymph node 
metastases, report location(s) by a standardized template.  
Table 5: Molecular imaging N classification for 18F-DCFPyL PET/CT.  
  
A standardized template for pelvic lymph node regions will be used (Table 6, Figure 4). This 
template covers the different regions usually approached when extended lymph node dissection 
is performed. Each region is encoded by a latin number; bilateral regions by a side (left/right, L/R).   
  
Region  
I  
II  
III  
IV  
V  
VI  
 
miN1/2 template  
Internal iliac  
External iliac  
Common iliac  
Obturator  
Presacral  
Other pelvic (specify)  
Report left/right  
Yes  
Yes  
Yes  
Yes  
No  
No  
Table 6: Pelvic Lymph node regions.  
  
  
  
  
Figure 4: miTNM standard template for pelvic lymph node regions. Transition to the extrapelvic 
region VII is indicated.  
  
Probability of nodal involvement increases with focal uptake, higher PSMA expression score 
and/or CT/MRI abnormalities such as increased short axis diameter, regional grouping, loss of 
fatty hilum, focal necrosis or increased contrast enhancement.   
PSMA-positive pitfalls such as focal uptake in an adjacent ureter, inflammation or lymphedema 
have to be ruled out.  
  


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Distant meta stases (M)  
  miM0    
  miM1    
    
D) Extra pelvic nodes and distant metastases (M)  
In accordance with clinicopathologic TNM, distant metastases will be separated into three 
categories: Any extra pelvic lymph nodes (miM1a); bone metastases (miM1b); organ metastases 
(miM1c) (Table 7).   
  
No distant metastasis  
Distant metastasis a Extrapelvic lymph node(s), additionally report location by a 
standardized miM1a template   
b Bone(s), additionally report pattern and involved bone(s) in case of unifocal or oligo 
metastatic  
c Other site(s), additionally report involved organ.  
Table 7: Molecular imaging N classification for 18F-DCFPyL PET/CT.  
  
miM1a nodes   
Location of miM1a nodes will be categorized based on a standard template into retroperitoneal, 
supradiaphragmatic or other regions (Table 8). Other regions need to be further specified in the 
final report.  
  
 
miM1a template  
 
VII  
Retroperitoneal  
No  
VIII  
Supradiaphragmatic  
Yes or No  
IX  
Other extra pelvic (specify)  
Yes or No  
Table 8: Extra-Pelvic Lymph node regions.  
  
miM1b bone metastasis   
Bone disease will be sub-categorized by pattern of involvement in unifocal, oligometastastic, 
disseminated disease and diffuse marrow involvement (Table 9).  
  
Abbreviation  
Pattern of bone involvement  
uni  
Unifocal  
oligo  
Oligometastatic (n≤3)  
diss  
Disseminated  
dmi  
Diffuse marrow involvement  
Table 9: Pattern of bone involvement.  
  
Oligometastatic bone involvement is diagnosed in case of three or less bone lesions (Schweizer 
et al., 2013). In case of unifocal or oligometastatic disease, involved bones will be specified. 
Pattern of bone involvement can have important implications for prognosis (Ost et al., 2014; 
Schweizer et al., 2013) and management (Tosoian et al., 2016). For instance unifocal disease 
may be targetable with curative intent by external-beam radiation therapy and diffuse marrow 
involvement indicates elevated risk for hematotoxicity after radionuclide therapy (Jong et al., 
2015; Parker et al., 2013; Rahbar et al., 2016).   


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Figure 5: miTNM categories and pattern of pelvic nodal, distant metastases and bone involvement 
for reporting prostate cancer stage by 18F-DCFPyL PET/CT. Tumor involvement is delineated in red. 
Abbreviations: uni, unifocal; oligo, oligometastatic; diss, disseminated; dmi, diffuse marrow involvement.  
  
In patients with organ involvement (miM1c) all involved organs need to be specified in the final 
report.  
  
Probability of bone or organ involvement increases with focal uptake, higher PSMA expression 
score and/or CT/MRI abnormalities. For bone metastases common CT findings include sclerotic, 
rarely lytic lesions with or without extraosseous extension; common MRI findings include low 
signal on unenhanced T1 images.  
  
PSMA-positive pitfalls such post-traumatic rib uptake, or non-prostate cancer related primary 
malignancies have to be ruled out (Rauscher et al., 2016).  
  
E) Level of Certainty  
  
Reporting level of certainty will be performed as previously proposed by Panicek et al (Panicek 
and Hricak, 2016) (Table 10).   
  
 
Term  
Numeric estimate  
 
Consistent with  
>90%  
Suspicious for/Probable/Probably ~75%  
 
Possible/Possibly  
~50%  
Less likely  ~25% Unlikely  
<10%  
 


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Table 10: Level of certainty.  
  
Certainty will substantially vary depending on uptake, location and CT or MRI findings. For 
instance at biochemical recurrence certainty of tumor localization will be substantially higher in 
case of focal uptake at a common location (e.g. internal iliac lymph node) as compared to an 
uncommon location (e.g. rib).   
  
Standardized wording for level of certainty will improve communication between the reader and 
the treating physician.   
  
1.1.8.3 Treatment Response Assessment  
1. miTNM  
a. Any decrease in miTNM class (ex: miT0N2M1b(uni) to miT0N1M1b(uni)) is considered 
partial response,   
b. Any increase in miTNM class (ex: miTr N1 (IVL) M0 to miT0 N2 M0) is considered 
progressive disease.   
c. Complete resolution on 18F-DCFPyL PET is complete response,   
d. No change in miTNM class is stable disease.  
  
2. total PSMA tumor volume   
Delineation of total PSMA tumor volume on PET by a yet to be determined algorithm.   
a. Decrease by 30% = PR,   
b. increase by 30% = PD,   
c. Volume = 0 = complete response,   
d. Otherwise stable disease.  
  
1.1.8.4 Measurements  
1) Primary Outcome Measurement:  
A separate analysis of initial versus subsequent management will be performed.  
  
The principal goal of this study is to evaluate the impact of 18F-DCFPyL PET/CT on patient 
management in patients with prostate cancer. The study includes a total of 3 questionnaires; 
Questionnaires 1 and 2 will be collected from referring physicians prior to and just after completion 
of the imaging study; these are designed to determine the intended patient management before 
and intended management changes after PET/CT.  
  
Patients can only be enrolled in the study if the pre-PET questionnaire (Q1) is completed.  
  
Treatment Modality Analysis: 3 categories of management changes will be evaluated:   
o no change  
o Inter-modality management changes (Major), i.e. change in modality or 
addition/removal of one or more modalities in the overall management  


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o Intra-modality management changes (Minor), i.e. same modality before and after 
PSMA PET/CT, however for instance:  
▪ 
Changes in Medical treatment   
▪ 
Changes in radiation approach   
▪ 
Changes in surgical approach  
▪ 
Addition/removal of concomitant ADT  
  
Disease stage based management Analysis:   
Treatment management will also be categorized as follow: A/ Local Prostate Fossa therapy, B/ 
Regional Pelvic therapy, C/ Lombo-aortic LN focused therapy, D/ Solitary LN or oligometastatic 
disease focused therapy and E/ Metastatic disease systemic therapy.  
  
Management change will be classified as: 1/ no change or 2/ change (addition/removal of one or 
more of these disease stage based treatment strategies)  
  
Questionnaire 3 will be mailed to referring physicians 3-6 months after completion of the imaging 
study to determine whether intended management changes were implemented.  
  
To assess the implemented treatment management, following methods will be used, in 
descending priority:  
1. Systematic electronic chart review when available  
2. Questionnaire   
3. Referring physician contact (email, phone or fax)  
4. Patient contact (email, phone or fax)  
  
2) Secondary Outcome Measurement:  
  
A) FOLLOW-UP IMAGING:  
  
All patients will be followed up 3-12 months with conventional imaging (dedicated CT, MRI and/or 
bone scan).  Interpretation of follow-up imaging will be performed by local read. For lesions that 
are reported in the blinded reads but not reported in the local evaluation of follow-up imaging, the 
local readers will be informed of the location of the lesions and follow-up will be performed for 
these additional lesions. Preferably, the follow-up conventional imaging should be the same 
modality/modalities as the initial staging work-up to allow for reproducible and accurate 
comparisons.    
  
Lymph Nodes lesions:  
18F-DCFPyL positive lymph nodes will be considered. Lymph nodes will be assessed by change 
in size.   
  
True positive:   
1) For patients undergoing systemic treatment (alone or in combination with targeted 
treatment): If on post-treatment follow-up imaging within 3-12 months, lymph nodes seen  


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on CT or MRI decrease by more than 30% in short axis diameter and PSA declines by 
more than 50%.  
▪ 
If PSA increases by more than 50% on systemic therapy, then a increase in the size 
of lesion by more than 20% will be considered a true positive lesion.  
2) In subjects with localized suspected lymph node(s) receiving targeted treatment without 
concomitant systemic treatment there are two ways to meet true positive disease:  
▪ 
If the subject shows a decrease of PSA by greater than 50% after targeted treatment 
and the lymph node does not enlarge (change in size less than 20% or less than 3 mm 
increase in short axis diameter) [OR]  
▪ 
If on post-treatment follow-up imaging within 3-12 months, lymph nodes seen on CT 
or MRI decrease by more than 30% in short axis diameter (with a minimum of 3 mm in 
change in size)  
3) For untreated patients: If on follow-up imaging within 3-12 months, lymph nodes seen on 
CT or MRI increase by more than 20% in short axis diameter (with a minimum of 3 mm in 
change in size).  
  
False positive:  
1) For patients undergoing systemic treatment (alone or in combination with targeted 
treatment): If on post-treatment follow-up imaging within 3-12 months, lymph nodes seen 
on CT or MRI increase by more than 20% in short axis diameter and PSA decreases by 
more than 50%.  
2) In subjects with localized suspected lymph node(s) receiving targeted treatment without 
concomitant systemic treatment there are two ways to meet false positive disease:  
▪ 
If the subject does not demonstrate a decrease of PSA by greater than 50% after 
targeted treatment [OR]  
▪ 
If on post-treatment follow-up imaging within 3-12 months, lymph nodes seen on CT 
or MRI increase by more than 20% in short axis diameter (with a minimum of 3 mm in 
change in size)  
3) For untreated patients: If on follow-up imaging within 3-12 months, lymph nodes seen on 
CT or MRI decrease by more than 30% in short axis diameter (with a minimum of 3 mm 
in change in size).  
  
If all regions in a patient/region do not meet criteria for either True positive or False positive 
disease, then the patient/region will be considered unevaluable for primary endpoint.  
  
Visceral lesions:  
18F-DCFPyL positive visceral lesions will be considered. Visceral lesions (non-lymph node soft 
tissue or organ) will be assessed by change in size.  
  
True positive:   
1) For patients undergoing systemic treatment (alone or in combination with targeted 
treatment): If on post-treatment follow-up imaging within 3-12 months, lesions seen on CT 
or MRI decrease by more than 30% in long axis diameter and PSA declines by more than 
50%.  


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▪ 
If PSA increases by more than 50% on systemic therapy, then a increase in the size 
of lesion by more than 20% will be considered a true positive lesion.  
2) In subjects with localized suspected lesions(s) receiving targeted treatment without 
concomitant systemic treatment there are two ways to meet true positive disease:  
▪ 
If the subject demonstrates a decrease of PSA by greater than 50% after targeted 
treatment [OR]  
▪ 
If on post-treatment follow-up imaging within 3-12 months, lesions seen on CT or MRI 
decrease by more than 30% in long axis diameter (with a minimum of 3 mm in change 
in size)  
3) For untreated patients: If on follow-up imaging within 3-12 months, lesions seen on CT or 
MRI increase by more than 20% in long axis diameter (with a minimum of 3 mm in change 
in size).  
  
False positive  
1) For patients undergoing systemic treatment (alone or in combination with targeted 
treatment): If on post-treatment follow-up imaging within 3-12 months, lesions seen on CT 
or MRI increase by more than 20% in long axis diameter and PSA decreases by more 
than 50%.  
2) In subjects with localized suspected lesions(s) receiving targeted treatment without 
concomitant systemic treatment there are two ways to meet false positive disease:  
▪ 
If the subject does not demonstrate a decrease of PSA by greater than 50% after 
targeted treatment [OR]  
▪ 
If on post-treatment follow-up imaging within 3-12 months, lesions seen on CT or 
MRI increase by more than 20% in long axis diameter (with a minimum of 3 mm in 
change in size).  
3) For untreated patients: If on follow-up imaging within 3-12 months, lesions seen on CT or 
MRI decrease by more than 30% in long axis diameter (with a minimum of 3 mm in change 
in size).  
  
If all regions in a patient/region do not meet criteria for either True positive or False positive 
disease, then the patient/region will be considered unevaluable for primary endpoint.  
  
Bone lesions   
18F-DCFPyL positive bone lesions will be considered.  
  
True positive:  
1) If there was a corresponding positive sclerotic lesion on the CT portion of the 68Ga-18F-
DCFPyL PET or on a separate CT obtained ≤ 30 days before or after the PET/CT in the 
same location as the PSMA uptake.  
2) If there is focal uptake seen in the same location as the PSMA uptake on the baseline 
bone scan performed within one month of 18F-DCFPyL PET.  
3) If there is a lesion noted in the same location as the PSMA uptake on the initial MRI 
performed within one month of 18F-DCFPyL.  


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4) If within 12 months follow-up CT demonstrates development of sclerosis in the same 
location as the PSMA uptake.  
5) If within 12 months follow-up MRI demonstrates a new bone lesion in the same location 
as the PSMA uptake.  
6) If within 12 months follow-up bone scan demonstrates new focal uptake in the same 
location as the PSMA uptake.  
7) In subjects with localized suspected bone lesion(s) receiving targeted treatment without 
concomitant systemic treatment:   
▪  If the subject demonstrates a decrease of PSA by greater than 50% after targeted 
treatment.  
  
False positive:   
1) In subjects with localized suspected bone lesion(s) receiving targeted treatment without 
concomitant systemic treatment:  
▪ If the subject does not demonstrate a decrease of PSA by greater than 50% after 
targeted treatment with curative intent (ie non-palliative radiation).  
2) If 18F-DCFPyL positive bone lesions do not meet the criteria for true positive findings, and 
appropriate correlative and follow-up imaging was acquired.  
  
If bone lesions do not meet criteria for either true positive or false positive disease listed above, 
then the patient/region will be considered unevaluable for primary endpoint.  
  
Prostate lesions:  
18F-DCFPyL positive prostate bed and prostate lesions will be considered:  
  
True positive:  
1) For patients undergoing systemic treatment (alone or in combination with targeted 
treatment): If on post-treatment follow-up imaging within 3-12 months, lesions seen on CT 
or MRI decrease by more than 30% in long axis diameter   
2) In subjects with localized suspected lesions(s) receiving targeted treatment without 
concomitant systemic treatment there are two ways to meet true positive disease:  
▪ 
If the subject demonstrates a decrease of PSA by greater than 50% after targeted 
treatment [OR]  
▪ 
If on post-treatment follow-up imaging within 3-12 months, lesions seen on CT or MRI 
decrease by more than 30% in long axis diameter (with a minimum of 3 mm in change 
in size)  
3) For untreated patients: If on follow-up imaging within 3-12 months, lesions seen on CT or 
MRI increase by more than 20% in long axis diameter (with a minimum of 3 mm in change 
in size).  
  
False positive:   
1) For patients undergoing systemic treatment (alone or in combination with targeted 
treatment): If on post-treatment follow-up imaging within 3-12 months, lesions seen on CT  


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or MRI increase by more than 20% in long axis diameter  and PSA decreases by more 
than 50%.  
2) In subjects with localized suspected lesions(s) receiving targeted treatment without 
concomitant systemic treatment there are two ways to meet false positive disease:  
▪ 
If the subject does not demonstrate a decrease of PSA by greater than 50% after 
targeted treatment [OR]  
▪ 
If on post-treatment follow-up imaging within 3-12 months, lesions seen on CT or 
MRI increase by more than 20% in long axis diameter (with a minimum of 3 mm in 
change in size)  
3) For untreated patients: If on follow-up imaging within 3-12 months, lesions seen on CT or 
MRI decrease by more than 30% in long axis diameter (with a minimum of 3 mm in change 
in size).  
If the lesion does not meet criteria for either True positive or False positive disease, then the 
lesion will be considered inevaluable for primary endpoint.  
  
B) HISTOPATHOLOGY/BIOPSY:  
  
Localization of lesions for histopathology/biopsy will be a classified by regions as specified in the 
miTNM framework. 18F-DCFPyL positive findings are aimed to be confirmed by histopathology 
(HP)/biopsy if clinically feasible. Pathology performed 60 days before the 18F-DCFPyL PET will 
be available for correlation. Histopathological procedures, biopsies and follow-up imaging will be 
performed as clinically indicated and as per institutional protocol.   
  
The following elective procedures may guide the investigator:  
  
Positive HP/Biopsy: Confirmed sites of metastatic or tumor involvement by histopathology/biopsy 
will be discussed with the responsible physician/surgeon.    
a) True Positive: lesion is positive on targeted biopsy/surgical sampling and is read as 
positive on 18F-DCFPyL PET.  
b) False Negative: lesion is positive on targeted biopsy/surgical sampling and is read as 
negative on 18F-DCFPyL PET.  
  
Negative HP/Biopsy: Patients with suspected tumor recurrence on 18F-DCFPyL PET with negative 
histopathology/biopsy will be handled as outlined below:  
1) Lymph nodes:  
i) For patients undergoing nodal dissection: Patients will be rescanned with dedicated 
CT, MRI or a repeat 18F-DCFPyL PET to determine if the suspicious 18F-DCFPyL 
positive node was removed.    
(1) If 18F-DCFPyL positive lymph node is still present, a repeat biopsy can be 
pursued if clinically feasible and applicable, or follow-up using imaging as 
described above will be performed.  
(2) If the corresponding node was removed, then this will be considered a False 
Positive.  


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ii) For patients undergoing needle biopsy: Images of the procedure will be reviewed to 
determine if the correct node was biopsied.    
(1) If the correct node was biopsied, then a negative biopsy will be considered a 
False Positive.  
(2) If the incorrect node was biopsied, then follow-up imaging as described above 
will be performed.  
  
2) Bone lesions:  Given the high rate of false negative biopsies for osseous metastases in 
patients with prostate cancer, patients with negative bone biopsies of PSMA PET positive 
lesions will be further evaluated:  
a) If pathology demonstrates an alternative diagnoses that is known to be PSMA positive 
(eg Renal Cell Carcinoma metastases, Paget’s disease), then this will be considered 
a False Positive.  
b) If pathology is indeterminate, then follow-up imaging as described above will be 
performed to determine if the lesion is a True Positive or False Positive.   
  
3) Although not routinely performed during standard practice, immunohistochemical staining 
for PSMA of tumor specimens (primary and lymph node metastases) may be performed, 
although not required.  
  
C) DEFINITIONS OF TRUE POSITIVE, FALSE POSITIVE, TRUE NEGATIVE, AND FALSE 
NEGATIVE PATIENTS AND REGIONS  
  
Pathology will be considered superior to imaging and clinical follow-up when available as 
described below. Patient and region level classification will be performed for each blinded reader, 
and be reported separately. The following criteria serve as a guide for interpretation. However not 
all findings on a lesions, region and patient level can be detailed here and investigators may 
deviate from these criteria in individual patients.  These will be recorded for each interpretation 
that is not described in this protocol for the definition of a region or patient.  
  
1) Patient level evaluation:   
  
a) True positive patient: A single region in a patient contains a true positive node either by 
pathology or imaging/clinical follow-up.  
i) For a patient to be considered a True Positive, only one region is required to have a 
true positive lesion as described above, unless one region is categorized as a false 
positive based on pathology.  This means that a single pathology false positive region 
outweighs regions with imaging/clinical follow-up true positive disease.  
ii) A patient will be considered a True Positive if one region contains a lesion that is True 
Positive, even if other regions are categorized as inevaluable or false positive based 
on imaging or clinical follow-up.  
  


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b) True negative patient: in the absence of True Positive or False Positive lesions, a patient 
will be considered a True Negative if there is pathology that is negative for disease and 
corresponding lesion is negative by 18F-DCFPyL PET.  
  
c) False positive patient:   
i) Pathology confirms a false positive lesion that is read as positive on 18F-DCFPyL PET.  
ii) In the absence of pathology: there are no true positive regions, and there is a region 
that is categorized as false positive based on imaging or clinical follow-up.  
  
d) False negative patient: in the absence of True Positive or False Positive lesions, a patient 
will be considered a False Negative if there is pathology that is positive for disease and 
corresponding lesion is negative by 18F-DCFPyL PET.  
  
2) Region level evaluation: Each patient will have four evaluable regions (Table 1: prostate 
bed, pelvis, extrapelvic soft tissue, and bone metastases).  Each region will be categorized 
as true positive or false positive as described above.  Regions without evidence of 18F-
DCFPyL positive disease or deemed unevaluable will not be included in the analysis.  
  
a) True positive region:   
i) Pathology confirms a 18F-DCFPyL avid lesion as a true positive in the region. ii) In the 
absence of pathology, clinical or imaging follow-up demonstrates a true positive lesion 
within the region independent of the presence of an inevaluable lesion or a false 
positive lesion (ie true positive disease will supersede a false positive lesion in the 
region based analysis if based on imaging/clinical follow-up).  
b) True negative region: in the absence of True Positive or False Positive lesions within a 
region, the region will be considered a True Negative if there is pathology that is negative 
for disease in the region and corresponding lesion is negative by 18F-DCFPyL PET.  
  
c) False positive region:  
i) Pathology confirms a 18F-DCFPyL avid lesion as a false positive in the region  
ii) In the absence of pathology, there are no true positive lesions in the region, and there 
is a false positive lesion by clinical or imaging follow-up.  
  
d) False negative region: in the absence of True Positive or False Positive lesions in a region, 
the region will be considered a False Negative if there is pathology that is positive for 
disease in the region and corresponding lesion is negative by 18F-DCFPyL PET.  
  
1.1.9 STATISTICAL CONSIDERATIONS  
1.1.9.1 Randomization  
No randomization will be done.  
1.1.9.2 Analysis Population  
Endpoints will be analyzed for the entire patient cohort and for treatment groups separately (Initial 
and subsequent).  


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1.1.9.3 Impact on Management Analysis Plan:   
The impact of 18F-DCFPyL PET on clinical management patients will be evaluated using 
descriptive statistics for both the treatment modality analysis and the disease stage based 
management analysis.  
1.1.9.4 Prognostic Value Analysis:  
Clinical outcome is defined by:  
o Radiographic PFS: time from inclusion to date until first site of disease is found to 
progress or death (whichever occurs first)  
a) Nodal and visceral disease is evaluated on cross-sectional imaging using  
RECIST 1.1/PCWG3 criteria  
b) Bone metastases are evaluated using bone scintigraphy and new lesions have to be 
confirmed on a second scan (2+2 rule) using PCWG3 criteria  
o Biochemical PFS: time from inclusion to date until PSA progression or death  
(whichever occurs first) (Scher et al., 2016)  
a) for  patients with PSA decline: Time from baseline to time the PSA increase to  
25% and 2 ng/ml above nadir which is confirmed by a second value ≥3 weeks  
later  
b) for patients without PSA decline: Time from baseline to time the PSA increase to 25% 
and 2 ng/ml above baseline  
o Overall survival: Time from inclusion to date of death.  
  
1.1.9.5 Positive predictive value (PPV) on a per-patient and per-region basis Analysis:  
PPVs on a per-patient and per-region-basis of 18F-DCFPyL PET for detection of tumor location 
confirmed by histopathology/biopsy, clinical and conventional imaging follow-up will be calculated 
and reported along with the corresponding two-sided 95% confidence intervals. The confidence 
intervals will be constructed using the Wilson score method. PPV will be reported for each of the 
three blinded readers independently.  
  
Detection rates on a per-patient basis of 18F-DCFPyL PET stratified by PSA value (0.2 - <0.5,  
0.5 - <1.0, 1.0 - <2.0, 2.0 - <5.0, ≥5.0) will be summarized in tabular format and compared 
between PSA strata using chi-square analysis.   
  
Detection rate is defined as number of patients with 18F-DCFPyL positive disease, independent 
of pathology, imaging or clinical follow-up.  A detection rate will be reported for each reader 
independently stratified by PSA.  
1.1.9.6Sample Size  


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Based on a previous study (Calais et al, 2017), we anticipate that 53% of patients will undergo an 
implemented change in management after 18F-DCFPyL PET/CT. Based on our previous 
experience and interim analysis, due to incomplete patient data, especially low turn-in rate from 
referring treating physician for post PET/CT intended treatment (Questionnaire 2),  a sample size 
of 400 patients would provide >90% power to determine whether the proportion of patients 
implementing change in management exceeds 40%, assuming an exact binomial test, and a one-
sided alpha of 0.025. A sample size of 400 patients is expected to produce a margin of error for 
the proportion of patients implementing change in management ranging from 6.9%, assuming a 
two-sided 95% confidence level. Sample size calculation was conducted in collaboration with the 
UCLA Department of Biostatistics (D. Elashoff, S. Vangala).  
1.1.9.7Accrual Estimates  
We plan to enroll 100 participants/year and this is achievable given our experience with other 
protocols and the expected support from the referring physicians within the Los Angeles region 
and beyond.  
  
1.1.10 CRITERIA FOR REMOVAL FROM STUDY  
The Principal Investigator may withdraw subjects from the study for one or more of the following 
reasons:  
▪ 
failure to follow the instructions of the Principal Investigator and/or study staff;  
▪ 
determination that continuing the participation could be harmful to the subject;  ▪  the study is 
cancelled   
▪ 
other administrative reasons.  
  
1.1.11 ADVERSE EVENTS AND REPORTING PROCEDURES  
1.1.11.1 Potential Adverse Events:  
The administration of the radioactive substance will feel like a slight pinprick if given by 
intravenous injection. Patients who are claustrophobic may feel some anxiety while positioned in 
the scanner. Also, some patients find it uncomfortable to hold one position for more than a few 
minutes. The subjects will not feel anything related to the radioactivity of the substance in their 
body. Because the radioactivity is very short-lived, the radiation exposure is low. The substance 
amount is so small that it does not affect the normal processes of the body.  
  
This research study involves exposure to radiation from one 18F-DCFPyL PET/CT. The effective 
dose from one typical 140 MBq administration of 18F-DCFPyL is 3.54 mSv. The effective dose 
from one CT attenuation scan is 4 mSv. Therefore, the effective dose from one 18F-DCFPyL 
PET/CT is 7.54 mSv, approximately equal to 15% of the limit that radiation workers (for example, 
a hospital x-ray technician) are allowed to receive in one year.  
1.1.11.2 Adverse Event Reporting  
We do not anticipate hazardous situations for the subjects as a result of this protocol. However, 
procedures will be in place for verification of correct radiopharmaceutical dose and route of 
administration (i.e., each dose will be double checked for dosimetry and quality by a researcher 
and technologist). The study Principal Investigator (PI) or his designee will report unanticipated 


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AEs to the VA IRB within 10 working days of becoming aware of the event (5 days if the event is 
life-threatening or resulted in death). If the principal investigator determines the unanticipated 
adverse device effect presents an unreasonable risk to subjects, the study will be terminated as 
soon as possible. Adverse events will be reported to the FDA.  
  
1.1.12 REGULATORY CONSIDERATIONS  
1.1.12.1 ClinicalTrials.gov  
The protocol will be registered on clinicaltrials.gov.  
1.1.12.2 Institutional Review of Protocol  
The protocol, the proposed informed consent and all forms of participant information related to 
the study (e.g. advertisements used to recruit participants) will be reviewed and approved by the 
VA IRB. Any changes made to the protocol will be submitted as a modification and will be 
approved by the IRB prior to implementation. The Principal Investigator will disseminate the 
protocol amendment information to all participating investigators.  
1.1.12.3 Data Management Plan  
The CRFs will be stored in a locked office in the Nuclear Medicine Department. During the clinical 
investigation, the Principal Investigator will evaluate the progress of the trial, including periodic 
assessments of data quality and timeliness, participant recruitment, accrual and retention, 
participant risk versus benefit, performance of trial sites, and other factors that can affect study 
outcome.   
  
 
  
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