Clinical trial NCT03113617
Conditions: Stage II Prostate Adenocarcinoma Stage III Prostate Adenocarcinoma Stage IV Prostate Adenocarcinoma
Sponsor: Andrei Iagaru
Start date: 2017-04-10; Completion date: 2021-12-19
Enrollment: 44 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This phase II trial studies how well gallium Ga 68-labeled gastrin-releasing peptide receptor (GRPR) antagonist BAY86-7548 (68Ga-RM2) positron emission tomography (PET)/computed tomography (CT) works in detecting regional nodal and distant metastases in patients with intermediate or high-risk prostate cancer. 68Ga-RM2 PET/CT scan may be able to see smaller tumors than the standard of care CT or magnetic resonance imaging scan.

Detailed description:
PRIMARY OBJECTIVES:

I. To evaluate 68Ga-RM2 PET/CT for detection of intermediate and high-risk prostate cancer prior to prostatectomy.

OUTLINE:

Patients receive 68Ga-RM2 intravenously (IV). Within 45-60 minutes, patients undergo a PET/CT scan. Patients may undergo a second PET/CT scan immediately after the first scan for attenuation correction. Patients may undergo also a repeat 68Ga-RM2 PET/CT scan after the completion of their treatment to evaluate response to therapy, if requested by the treating physician.

After completion of study, patients are followed up at 24-48 hours and within 3-12 months.

Arms: arm 1: Patients receive 68Ga-RM2 IV. Within 45-60 minutes, patients undergo a PET/CT scan. Patients may undergo a second PET/CT scan immediately after the first scan for attenuation correction. Patients may undergo also a repeat 68Ga-RM2 PET/CT scan after the completion of their treatment to evaluate response to therapy, if requested by the treating physician.
Interventions: intervention 1: Computed Tomography intervention 2: Gallium Ga 68-labeled GRPR Antagonist BAY86-7548 intervention 3: Laboratory Biomarker Analysis intervention 4: Positron Emission Tomography
Intervention descriptions: intervention 1: Undergo PET/CT intervention 2: Given IV intervention 3: Correlative studies intervention 4: Undergo PET/CT

Protocol documents:
Prot_SAP_002.pdf: 
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68Ga-RM2 PET/MRI for Detection of Regional Nodal and Distant Metastases in Patients 
with Intermediate and High-Risk Prostate Cancer 
Principal Investigator / Protocol Director 
Andrei Iagaru, MD 
300 Pasteur Drive, 
Stanford, CA 94305 
Phone:  650-725-4711 
Fax:  650-498-5047 
Email:  aiagaru@stanford.edu 
Co-investigators 
Farshad Moradi MD, PhD 
300 Pasteur Dr, 
Stanford, CA  94305  
Phone:  650-725-4711 
Email:   fmoradi@stanford.edu  
Pejman Ghanouni, MD, PhD 
1201 Welch Road, 
Stanford, CA 94305  
Phone:  650-498-4485 
Email:  ghanouni@stanford.edu 
Geoffrey Sonn, MD 
875 Blake Wilbur Dr;  
Stanford, CA  94305 
Email:  gsonn@stanford.edu 
Guido Davidzon, MD 
300 Pasteur Dr, 
Stanford, CA  94305  
Phone:  650-725-4711 
Email:   gdavidzon@stanford.edu  
Carina Mari Aparici, MD 
300 Pasteur Dr, Room 
Stanford, CA  94305  
Phone:  650-725-4711 
Email:  drmari@stanford.edu 
Biostatistician 
 PhD 
Stanford, CA 94305 
Phone: 
Email: 
@stanford.edu 
Study Coordinator 
 or designate 
Phone: 
Email:  
@stanford.edu 
SRC Protocol / Version 5 / Version Date13 December 2021 
protocol IRB-40373 
NCT03113617 


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TABLE OF CONTENTS 
PROTOCOL SYNOPSIS ........................................................................................................... 4 
SCHEMA ................................................................................................................................... 4 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS ...................................................... 5 
1. OBJECTIVE ........................................................................................................................ 6 
 Specific Aim ........................................................................................................................ 6 
2. BACKGROUND AND SIGNIFICANCE ............................................................................... 6 
 Rationale ............................................................................................................................ 7 
 Study Design ...................................................................................................................... 9 
3. PARTICIPANT SELECTION AND ENROLLMENT PROCEDURES ...................................10 
 Inclusion Criteria ................................................................................................................10 
 Exclusion Criteria ...............................................................................................................10 
 Informed Consent Process ................................................................................................10 
 Study Timeline ...................................................................................................................10 
    Primary Completion: ......................................................................................................10 
    Study Completion: .........................................................................................................10 
4. IMAGING AGENT INFORMATION ....................................................................................10 
 Study Agent .......................................................................................................................10 
 Specify the source of the study agent ................................................................................11 
 Describe how the agent will be requested and provide mailing address and phone number.
 11 
 Agent Accountability ..........................................................................................................11 
5. IMAGING SPECIFICS .......................................................................................................11 
 Modality or Modalities to be used .......................................................................................11 
 Details of Imaging (i.e. dynamic, static, number of scans, etc.) ..........................................11 
6. STUDY PROCEDURES ....................................................................................................12 
 Criteria for Removal from Study .........................................................................................12 
 Alternatives ........................................................................................................................12 
7. STUDY CALENDAR ..........................................................................................................12 
8. ADVERSE EVENT REPORTING .......................................................................................12 
9. REGULATORY CONSIDERATIONS .................................................................................12 


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 Institutional Review of Protocol ..........................................................................................12 
 Data Management Plan .....................................................................................................13 
10. MEASUREMENTS ..........................................................................................................13 
 Study Endpoints.................................................................................................................13 
    Primary endpoint: ..........................................................................................................13 
    Secondary endpoint: .....................................................................................................13 
    Exploratory endpoint:.....................................................................................................13 
 Image interpretation: ..........................................................................................................13 
    68Ga-RM2 PET/CT:........................................................................................................13 
 Follow-up: ..........................................................................................................................14 
 Statistical analysis: ............................................................................................................14 
11. ADVERSE EVENTS AND REPORTING PROCEDURES ...............................................15 
 Potential Adverse Events ...................................................................................................15 
Appendix: Inclusion/Exclusion Criteria Checklist ................................................................17 
REFERENCES: ........................................................................................................................19 
 


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PROTOCOL SYNOPSIS 
 
TITLE 
68Ga-RM2 PET/MRI for Detection of Regional Nodal 
and Distant Metastases in Patients with Intermediate 
and High-Risk Prostate Cancer 
STUDY PHASE 
Phase 2 
INDICATION 
Prostate cancer 
INVESTIGATIONAL PRODUCT 
OR PROCEDURE 
68Ga-RM2 
PRIMARY OBJECTIVE(S) 
To evaluate 68Ga-RM2 PET/MRI for detection of 
regional nodal and distant metastases in patients with 
intermediate and high-risk prostate cancer scheduled to 
undergo prostatectomy with lymph node dissection. 
SAMPLE SIZE  
90 participants 
GOALS 
To allow the referring physicians in the GU Oncology 
group to provide their patients a specific molecular 
imaging test for prostate cancer that is currently used 
outside of the United States. 
To refine the PET/MRI protocols in the setting of initial 
staging of patients with intermediate and high risk 
prostate cancers. 
 
 
SCHEMA 
 
 
 
 
Eligible participant with prostate cancer 
68Ga-RM2 PET/MRI


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LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
 
Ga-68 
Gallium-68 
IRB 
Institutional Review Board 
IV 
Intravenous 
PET/MRI 
Positron emission tomography – magnetic resonance imaging 
SUV 
Standardized Uptake Value 
GRPr 
Gastrin releasing peptide receptor 
BPH 
Benign prostate hypertrophy 
PSA 
Prostate specific antigen 
PSMA 
Prostate specific membrane antigen 
 


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1. OBJECTIVE 
 
1.1 Specific Aim 
To evaluate 68Ga-RM2 PET/MRI for detection of intermediate and high-risk prostate cancer prior 
to prostatectomy. 
 
Figure 1. Chemical structure of 68Ga-RM2 
2. BACKGROUND AND SIGNIFICANCE 
Data from the American Cancer Society suggests that for 2015 in the United States prostate 
cancer will continue to be the leading non-cutaneous cancer diagnosis in males with 220,800 
estimated new cases, and has the second highest mortality (after lung) with 27,540 estimated 
deaths (1). Initial screening and diagnosis relies on the digital rectal exam (DRE), prostate 
specific antigen (PSA), and transrectal ultrasound-guided core biopsies (2, 3). Subsequent 
treatment is multifaceted and may involve observation, surgery (prostatectomy), radiation 
therapy (external beam or brachytherapy), hormonal therapy, chemotherapy, or a combination 
of these (4-6).  
The choice of treatment directly depends on the initial staging, as well as the patient’s age, 
co-morbidities, and preferences. Prostate cancer staging is based on the 
tumor-node-metastases (TNM) classification. As outlined in the National Comprehensive 
Cancer Network guidelines, those patients requiring staging for additional therapy would need a 
bone scan and pelvic CT or MRI if the T-stage is greater than 2 or if the PSA or Gleason score 
is elevated (> 20 ng/mL and > 8, respectively). The CT or MRI is primarily used to identify 
locoregional lymph nodes (thereby altering the N-stage), while the bone scan is primarily used 
to identify osseous metastatic disease (thereby altering the M-stage). In particular, the 
prognostic importance of bone metastases in patients with prostate cancer has been 
established. Patients with an abnormal bone scan at the time of diagnosis have a mortality rate 
twice as high as patients with normal bone scans (7). 
However, at initial staging the issue is detection of pelvic and retroperitoneal small lymph node 
metastases that don’t trigger size criteria on CT and MRI; bone metastases are a rare 
presentation.   
Other tracers, such as 18F- or 11C-labeled choline and [11C]-acetate, are used mainly for the 
diagnosis of recurrent (8-10) or metastatic (11) prostate cancer. Their feasibility in primary 


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diagnosis is limited because of uptake in benign tissue such as benign prostatic hyperplasia or 
inflammatory lymph nodes (12, 13). 
Although choline based PET/CT is widely used outside the US for imaging prostate cancer, 
there have been numerous studies reporting a low sensitivity and specificity, especially at low 
prostate specific antigen (PSA) levels (14, 15). Consequently, improved imaging of prostate 
cancer is necessary. One novel promising method is PET imaging with 18F-FACBC, a new 
synthetic amino acid. Recent evaluations by Nanni et al. indicate that this tracer might be 
superior when compared to choline PET/CT (16). However, recent work indicates that 
18F-FACBC uptake in prostate cancer is similar to that in BPH nodules (17). Prostate-specific 
membrane antigen (PSMA) continues to elicit high interest. This cell surface protein is 
significantly overexpressed in prostate cancer cells when compared to other PSMA-expressing 
tissues such as kidney, proximal small intestine or salivary glands. It therefore provides a 
promising target for prostate cancer-specific imaging. Recently methods have been developed 
to label PSMA ligands with 68Ga and 18F. Initial experience suggests that these novel tracers 
can detect prostate cancer relapses and metastases with high contrast by binding to the 
extracellular domain of PSMA, followed by internalization (18, 19). However, these promising 
agents do not detect all recurrences.  
Consequently, improved imaging of prostate cancer continues to be an area of unmet clinical 
need.  68Ga-labeled DOTA-4-amino-1-carboxymethyl-piperidine-D-Phe-Gln-Trp-Ala-Val-Gly-
His-Sta-Leu-NH2 (68Ga-RM2, formerly also known as BAY86-7548 or 68Ga-DOTA-Bombesin) is 
a synthetic bombesin receptor antagonist, which targets gastrin-releasing peptide receptors 
(GRPr) (20). GRPr proteins are highly overexpressed in several human tumors, including 
prostate cancer (21). Because of their low expression in BPH and inflammatory prostatic tissues 
(22, 23), imaging of GRPr has potential advantages over current choline- and acetate-based 
radiotracers. Indeed, preclinical studies using BAY86-7548 have shown a high and persistent 
tracer uptake in mice bearing PC-3 tumor xenografts, which represent androgen-independent 
human prostate cancer with high GRPr expression (24). 
Clinicaltrials.gov  
This study is registered on ClinicalTrials.gov as NCT03113617. 
2.1 Rationale 
In this study, we propose to use a well-established PET isotope, Gallium-68 (68Ga), bound to a 
bombesin receptor antagonist, 68Ga-RM2, which has high affinity for gastrin-releasing peptide 
receptors. GRPr proteins are highly overexpressed in several human tumors, including prostate 
cancer (21). Because of their low expression in BPH and inflammatory prostatic tissues (22, 23), 
imaging of GRPr has the potential to improve the lesion detection in prostate cancer. Therefore, 
we propose the following aim: 
• 
To evaluate 68Ga-RM2 PET/MRI for detection of intermediate and high-risk prostate 
cancer prior to prostatectomy 


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The first-in-human study investigated the safety, tolerability, metabolism, pharmacokinetics, 
biodistribution, and radiation dosimetry of 68Ga-RM2. Five healthy men underwent dynamic 
whole-body PET/CT after an intravenous injection of 68Ga-RM2 (138 ± 5 MBq). Besides total 
radioactivity, plasma samples were analyzed by radio–high-performance liquid chromatography 
for metabolism of the tracer. Dosimetry was calculated using the OLINDA/EXM software. The 
organs with the highest absorbed doses were the urinary bladder wall (0.62 mSv/MBq) and the 
pancreas (0.51 mSv/MBq). The mean effective dose was 0.051 mSv/MBq. 68Ga-RM2 was well 
tolerated by all subjects. The authors concluded that the intravenously injected 68Ga-RM2 is 
safe, and rapid metabolism is demonstrated. A 150-MBq injection of 68Ga-RM2 results in an 
effective dose of 7.7 mSv, which could be reduced to 5.7 mSv with frequent bladder voids (25).  
 
Figure 2: Coronal (A) and axial views (B and C) of 68Ga-RM2 PET/CT in patient no. 8 with prostate 
cancer metastasis to multiple lymph nodes. Two normal-sized (less than 10 mm) nodes above the aortic 
bifurcation indicated with red arrow showed increased uptake of tracer, SUVmax 6.2 and 6.3. In addition, 
one left parailiac node, SUVmax 12.7, (B) and two right parailiac nodes, SUVmax 6.1 and 4.7, (C) 
showed increased uptake of 68Ga-RM2. These five lymph nodes were histologically confirmed as 
metastases at surgery. Green arrows point to ureters, which can be easily distinguished on anatomic CT. 
In the first study with 68Ga-RM2 in patients with prostate cancer, 14 men scheduled for radical 
prostatectomy (n = 11) or with biochemical recurrence after surgery or hormonal therapy (n = 3) 
were enrolled. The patients received an intravenous injection of 68Ga-RM2 followed by over 
60-minute dynamic imaging of prostate gland (n = 10) and/or subsequent whole-body imaging 
(n = 14). The visual assessment of PET/CT images included evaluation of intraprostatic 


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(12 subsextants) and pelvic nodal uptake of 68Ga-RM2 in 11 surgical patients and detection of 
potential metastatic foci in all patients. In patients with biochemical recurrence, results were 
compared with those of either 11C-acetate (n = 2) or 18F-fluoromethylcholine (n = 1) PET/CT. 
The authors reported a sensitivity, specificity, and accuracy of 88%, 81% and 83%, respectively, 
for detection of primary prostate cancer and sensitivity of 70% for metastatic lymph nodes using 
histology as gold standard (26). In our experience, 68Ga-RM2 compared favorably against 
68Ga-PSMA (27). 
2.2 Study Design 
This is a prospective, single center, single-arm study enrolling 90 participants with intermediate 
and high-risk prostate cancer. Eligible participants will undergo baseline assessments at 
enrollment. Study participants will receive 68Ga-RM2 and undergo a PET/MRI scan. All patients 
will first be seen by a Stanford Cancer Institute physician and then referred if appropriate on 
clinical grounds to Dr. Iagaru or his colleagues for this study.  The following steps will take 
place. 
1. After signed the informed consent document, participants will be given a copy of the 
signed form 
2. Participant will be asked to drink 1 to 2 glasses of water before arrival at the clinic 
3. Participants will be weighed and vital signs (heart rate and blood pressure) will be 
recorded 
4. Study personnel (eg, technologist) will verify subject identify;  radiopharmaceutical 
identity;  dose;  and administration route.  Participant will be injected IV with 
140 MBq ± 20% of 68Ga-RM2 
5. Participant will void immediately prior to the scan 
6. Approximately 50 to 100 minutes after the radiopharmaceutical IV administration, data 
acquisition will begin in the pelvic region and move toward the head.  First, localizer MRI 
scans will be performed to define the table positions.  After correct positioning of the 
spatial acquisition windows is ensured, the combined PET/MRI acquisition will be 
initiated with 3 to 5 table positions at a 4-min acquisition time per table position. 
7. Vital signs (heart rate and blood pressure) will be recorded again at the completion of 
the study. 
8. Participants will be dismissed. 
9. Participants will be contacted at 24 to 72 hours following the scan in order to capture 
potential late occurring Adverse Events. 
The 68Ga-RM2 PET/MRI may be repeated at the completion of treatment to evaluate response 
to therapy, if requested by the treating physician.  


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3. PARTICIPANT SELECTION AND ENROLLMENT PROCEDURES 
3.1 Inclusion Criteria 
• 
Older than 18 year-old 
• 
Biopsy proven prostate adenocarcinoma 
• 
Planned prostatectomy with lymph node dissection 
• 
Intermediate to high-risk disease (as determined by elevated PSA [PSA>10], T-stage 
[T2b or greater], Gleason score [Gleason score > 6] or other risk factors) 
• 
Able to provide written consent 
• 
Karnofsky performance status of 50 (or ECOG/WHO equivalent) 
• 
Diagnostic CT or MRI performed within 30 days prior to the 68Ga-RM2 PET 
3.2 Exclusion Criteria 
• 
Inability to lie still for the entire imaging time (approximately 30 minutes) 
• 
Inability to complete the needed investigational and standard-of-care imaging 
examinations due to other reasons (severe claustrophobia, radiation phobia, etc.) 
• 
Any additional medical condition, serious intercurrent illness, or other extenuating 
circumstance that, in the opinion of the Investigator, may significantly interfere with study 
compliance 
• 
Metallic implants (contraindicated for MRI) 
3.3 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. 
The participant must receive a copy of the signed and dated consent document. The original 
signed copy of the consent document must be retained in the medical record or research file.  
3.4 Study Timeline 
3.4.1 Primary Completion: 
The study will reach primary completion 36 months from the time the study opens to accrual. 
3.4.2 Study Completion: 
The study will reach study completion 48 months from the time the study opens to accrual. 
4. IMAGING AGENT INFORMATION 
4.1 Study Agent  
We will use 68Ga-RM2 as the PET radiopharmaceutical. The administered dosage is 
140 MBq ± 20% i.v.  


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4.2 Specify the source of the study agent  
Molecular Imaging Program at Stanford 
Satellite Radiochemistry Facility  
300 Pasteur Dr, 
 
Stanford, CA 94305  
4.3 Describe how the agent will be requested and provide mailing address and 
phone number. 
Ordered in Radiology Information System (RIS), address per above. 
4.4 Agent Accountability 
RIS is password protected and part of the electronic medical records. 
5. IMAGING SPECIFICS  
5.1 Modality or Modalities to be used 
PET/MRI 
5.2 Details of Imaging (i.e. dynamic, static, number of scans, etc.) 
We will use 68Ga-RM2 as the PET radiopharmaceutical. The administered dosage is 
140 MBq ± 20% i.v.  
A localizer MRI scan will be performed at 45 minutes after injection of 140 MBq ± 20% of 
68Ga-RM2 to define the table positions.  After correct positioning of the spatial acquisition 
windows is ensured, the combined PET/MRI acquisition will be initiated with 3 to 5 table 
positions at a 4-min acquisition time per table position.  A volumetric T1 acquisition with 
fat-water separation and motion correction to enable free-breathing will be obtained at each 
table position and used for the generation of attenuation maps and for anatomic allocation of the 
PET results.  Simultaneously with the start of the T1 MRI sequence, the PET acquisition will 
start at the same table position, thus ensuring optimal temporal and regional correspondence 
between MRI and PET data.  The PET acquisition time will be 4 min per table position, taking 
delayed acquisition times and radioactive decay into account.  As the T1 will take less than 
4 minutes, a rapid diffusion weighted MRI will also be performed.  After completion of the PET 
acquisition, the table will be moved to the next table position and the procedure will be repeated.  
Upon completion of the PET acquisition for all stations, volumetric post-contrast T1- and 
T2-weighted MR images may be obtained at multiple stations as needed. 
The PET emission scan is corrected using segmented attenuation data of the MRI scan.  The 
PET images are reconstructed with a standard iterative algorithm.  All images are reformatted 
into axial, coronal, and sagittal views and viewed with the software provided by the 
manufacturer (AW, GE Medical Systems).  


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6. STUDY PROCEDURES 
6.1 Criteria for Removal from Study 
The Protocol Director may withdraw subjects from the study for one or more of the following 
reasons: failure to follow the instructions of the Protocol Director and/or study staff; 
determination that continuing the participation could be harmful to the subject; the study is 
cancelled or other administrative reasons. 
6.2 Alternatives 
The alternative is to not participate in the study.  
7. STUDY CALENDAR 
 
Pre-Study 
Week 1 
24 - 72 Hours Post-Study 
12 Months 
Informed consent 
X 
 
 
 
Demographics 
X 
 
 
 
Medical history 
X 
 
 
 
Follow-up Call to Participant 
 
 
X 
 
68Ga-RM2 PET/MRI 
 
X 
 
 
Data analysis 
 
 
 
X 
 
8. 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 
AEs related to the Stanford CCTO Safety Coordinator within 10 working days of becoming 
aware of the event (5 days if the event is life-threatening or resulted in death) using the Adverse 
Events Communication Form. 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, but no later than 5 working days after the PI makes the determination and no later 
than 15 working days after first receiving notification of the effect. 
9. REGULATORY CONSIDERATIONS 
9.1 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 
Stanford IRB. Any changes made to the protocol will be submitted as a modification and will be 
approved by the IRB prior to implementation. The Protocol Director will disseminate the protocol 
amendment information to all participating investigators. 


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9.2 Data Management Plan 
The Stanford Cancer Institute Data and Safety Monitoring Committee (DSMC) will audit study 
related activities to determine whether the study has been conducted in accordance with the 
protocol, local standard operating procedures, FDA regulations, and Good Clinical Practice 
(GCP).  This may include review of regulatory binders, case report forms, eligibility checklists, 
and source documents.  In addition, the DSMC will regularly review serious adverse events and 
protocol deviations associated with the research to ensure the protection of human subjects.  
Results of DSMC audits will be communicated to the IRB and the appropriate regulatory 
authorities at the time of continuing review, or in an expedited fashion, as needed. 
10. MEASUREMENTS 
10.1 Study Endpoints 
10.1.1 Primary endpoint: 
i. 
Sensitivity, specificity, positive and negative predictive value of 68Ga-RM2 
PET for the detection of regional nodal metastases compared to pathology at 
radical prostatectomy on a per patient basis.  
10.1.2 Secondary endpoint: 
i. 
Sensitivity, specificity, negative and positive predictive value for detection of 
regional nodal metastases in comparison to cross sectional imaging 
performed contemporaneously with the 68Ga-RM2 PET.  
10.1.3 Exploratory endpoint: 
i. 
One year PSA progression free survival, comparing patients with and without 
pelvic nodal metastases.  
ii. 
Correlation between SUVmax from 68Ga-RM2 PET and short axis diameter of 
nodal disease on cross sectional imaging correlate to presence of true 
pathology.  
iii. 
Incidence of osseous and distant metastatic lesions.  
10.2 Image interpretation:  
10.2.1 68Ga-RM2 PET/MRI: 
The PET/MRI scans will be interpreted by ABNM certified Nuclear Medicine physicians and 
ABR-certified radiologists. Consensus read will be obtained for each scan. Each lesion will be 
tabulated and a comparison of lesion detection by each scanner will be conducted. 
Visual interpretation of PET data:  
Regions of suspected disease will be graded on a two-point scale by each reader (0 = Negative 
or 1 = Positive). A region will be judged as positive if at least one lesion in this region is visually 
positive.  


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i. 
Lymph nodes will be considered positive if the 68Ga-RM2 uptake is focal and 
greater than adjacent background. Pelvic lymph nodes will be sub-classified 
according to their localization as follows: R/L obturator, R/L external iliac, R/L 
internal iliac and other (total of 7 subgroups). 
ii. 
Visceral lesions will be considered positive if the 68Ga-RM2 uptake is focal 
and greater than physiologic background activity of the involvement organ or 
anatomic site.  
iii. 
Bone lesions will be considered positive if the 68Ga-RM2 uptake is focal and 
greater than physiologic bone marrow.  
10.3 Follow-up: 
a. Prostatectomy: patients without evidence of 68Ga-RM2 PET positive nodal or 
metastatic disease noted on imaging will undergo radical prostatectomy.  If a 
68Ga-RM2 PET positive regional pelvic node is noted, the urologist will be informed 
of the location of the suspicious node and the patient will undergo prostatectomy with 
nodal dissection. 
i. 
Patients with nodes seen on 68Ga-RM2 PET without positive nodes on 
pathology, will be rescanned with MRI or CT to determine if the suspicious 
node was thought to be removed.  A 68Ga-RM2 PET may be repeated as well.  
b. If sites of 68Ga-RM2 PET positive osseous or distant metastatic lesions are noted, 
the urologist will be informed, and further evaluation including further imaging (bone 
scan, 18F NaF PET, CT or MRI cross section imaging) or targeted biopsy will be 
performed in order to restage the patient prior to the decision regarding whether or 
not a prostatectomy will be performed as per the responsible surgeon and standard 
of clinical care. 
c. The results of this research scan will be provided to the treating physician who may, 
at their discretion, decide to conduct further imaging scans and/or biopsies.  The type 
and details of these additional scans are not specified, and are at the treating 
physician’s discretion.  
d. Pathology: Specimens from prostatectomy will be evaluated for the presence of 
nodal metastasis.  This will be reported on a per patient basis as positive or negative.   
i. 
If possible, the presence of nodal disease on a per region basis (inguinal, 
left/right obturator, external and internal iliac, paraaortic nodal regions) should 
be performed.  This data will be grouped for subanalysis. 
ii. 
The number of nodes counted on pathology will also be recorded.  
10.4 Statistical analysis: 
a. Sample size:  90 patients in total. The power analysis is based on the comparison of 
sensitivity between conventional imaging and 68Ga-RM2 PET.  
i. 
30% of intermediate to high-risk patients have nodal metastases at 
prostatectomy. 


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ii. 
Conventional imaging has a 45% detection sensitivity for nodal metastases 
on a per patient basis (2).  
iii. 
68Ga-RM2 PET has a 60% detection sensitivity for nodal metastases on a per 
patient basis.  
b. Statistical analysis: The sensitivity, specificity, positive and negative predictive value 
of 68Ga-RM2 PET for the detection on a per patient basis will be determined using 
the below criteria: 
i. 
True positive patient: 
1. 
68Ga-RM2 PET positive for regional nodes; pathology at 
prostatectomy positive for regional nodes. 
2. 
68Ga-RM2 PET positive for regional nodes, pathology negative for 
regional nodes, imaging after prostatectomy demonstrates node was 
not removed at surgery, and follow-up biopsy or imaging 
demonstrates presence of nodal disease. 
a. Criteria for positive node on follow-up imaging: imaging within 
3-12 months, the node decreases by more than 30% (for patients 
undergoing systemic treatment or focal therapy at this site) or 
increase by more than 20% in short axis diameter in the absence 
of treatment (with a minimum of 3 mm in change in size). 
ii. 
True negative patient: 
1. 
68Ga-RM2 PET negative for regional nodes; pathology at 
prostatectomy negative for regional nodes. 
iii. 
False positive patient: 
1. 
68Ga-RM2 PET positive for regional nodes, pathology at 
prostatectomy is negative, and imaging after prostatectomy 
demonstrates that node is no longer present. 
iv. 
False negative patient: 
1. 
68Ga-RM2 PET negative for regional nodes, but pathology at 
prostatectomy is positive. 
v. 
Non-evaluable: 
1. 
68Ga-RM2 PET positive for regional nodes, pathology negative for 
regional nodes, imaging after prostatectomy demonstrates node was 
not removed at surgery, and no definitive follow-up is available. 
2. Patients with extrapelvic nodal metastases will not be included in this 
analysis if patients do not undergo prostatectomy. 
11. ADVERSE EVENTS AND REPORTING PROCEDURES 
11.1 Potential Adverse Events 
The administration of the radioactive substance will feel like a slight pinprick when given by i.v. 
injection. Patients who are claustrophobic may feel some anxiety while positioned in the 


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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. This radiation exposure is for research 
purposes only. The amount of radiation from one 68Ga-RM2 PET is 4.76 mSv, approximately 
equal to 10% of the limit that radiation workers (for example, a hospital x-ray technician) are 
allowed to receive in one year. There is no radiation exposure from MRI. Therefore, the total 
radiation exposure is 4.76 mSv. This amount of radiation involves minimal risk and is necessary 
to obtain the research information desired.  
 


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Appendix: Inclusion/Exclusion Criteria Checklist  
Protocol Title: 
68Ga-RM2 PET/MRI for Detection of Regional Nodal and Distant 
Metastases in Patients with Intermediate and High-Risk Prostate Cancer 
Protocol Number: 
IRB-40373 
Principal Investigator: 
Andrei Iagaru, MD 
 
Inclusion Criteria – “Yes” must be checked to be eligible 
(From IRB approved protocol) 
Yes 
No 
Supporting 
Documentation 
1. Older than 18 year-old 
☐ 
☐ 
☐ 
2. Biopsy proven prostate adenocarcinoma 
☐ 
☐ 
☐ 
3. Planned prostatectomy with lymph node dissection 
☐ 
☐ 
☐ 
4. Intermediate to high-risk disease (as determined by 
elevated PSA [PSA>10], T-stage [T2b or greater], 
Gleason score [Gleason score > 6] or other risk factors) 
☐ 
☐ 
☐ 
5. Able to provide written consent 
☐ 
☐ 
☐ 
6. Karnofsky performance status of  50 (or ECOG/WHO 
equivalent) 
☐ 
☐ 
☐ 
7. Diagnostic CT or MRI performed within 90 days prior to 
68Ga-RM2 PET 
☐ 
☐ 
☐ 
 
*All subject files must include supporting documentation to confirm subject eligibility.  The method of confirmation can 
include, but is not limited to, laboratory test results, radiology test results, subject self-report, and medical record 
review.   
Exclusion Criteria – “No” must be checked to be eligible 
(From IRB approved protocol) 
Yes 
No 
Supporting 
Documentation 
1. Inability to lie still for the entire imaging time 
(approximately 30 minutes) 
☐ 
☐ 
☐ 
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 intercurrent 
illness, or other extenuating circumstance that, in the 
opinion of the Investigator, may significantly interfere 
with study compliance 
☐ 
☐ 
☐ 
4. Metallic implants (contraindicated for MRI) 
☐ 
☐ 
☐ 


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i. 
Statement of Eligibility 
By signing this form of this trial I verify that this subject is [☐eligible / ☐ ineligible] for participation in the study. This 
study is approved by the Stanford Cancer Institute Scientific Review Committee, the Stanford IRB, and has finalized 
financial and contractual agreements as required by Stanford School of Medicine’s Research Management Group.   
Treating Physician Signature: 
Date: 
Printed Name: 
 
Study Coordinator Signature: 
Date: 
Printed Name: 
Secondary Reviewer Signature: 
Date: 
Printed Name: 


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