Clinical trial NCT02678351
Conditions: Stage II Prostate Adenocarcinoma Stage III Prostate Adenocarcinoma
Sponsor: Andrei Iagaru
Start date: 2016-04-18; Completion date: 2021-12-01
Enrollment: 74 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This phase 2-3 trial studies the utility of 68-gallium (68Ga)-prostate-specific membrane antigen 11 (PSMA-11) positron emission tomography/magnetic resonance imaging (PET/MRI) to find tumors in patients with prostate cancer who are undergoing resection surgery for prostate cancer that is prognostically expected to spread quickly (intermediate-risk) or is likely to come back or spread (high-risk). Diagnostic procedures, such as PET/MRI, may help find and diagnose prostate cancer, and reveal out how far the disease has spread. Radioactive drugs, such as 68Ga-PSMA-11, may bind to tumor cells that have specific receptors, and may allow doctors to see smaller tumors than the standard of care contrast-enhanced computed tomography (CT) or MRI scan.

Detailed description:
OBJECTIVES:

1. To evaluate 68Ga-PSMA-11 PET/MRI for detection of tumor metastases in patients with intermediate and high-risk prostate cancer scheduled to undergo prostatectomy with lymph node dissection.
2. To assess sensitivity (positive predictive value) and specificity (negative predictive value) of 68Ga-PSMA-11 PET/MRI for the detection of regional nodal metastases compared to pathology at radical prostatectomy.

OUTLINE:

Participants will receive 68Ga-PSMA-11 intravenously (IV). Patients then undergo PET/MRI after 45 minutes of administration of radiopharmaceutical injection.

After completion of study, patients are followed up at 24 to 48 hours.

Arms: arm 1: Patients receive 68Ga-PSMA-11 IV. Patients then undergo PET/MRI after 45 minutes of administration of radiopharmaceutical injection.
Interventions: intervention 1: 68Ga-PSMA-11 intervention 2: Magnetic resonance imaging (MRI) intervention 3: Positron Emission Tomography (PET)
Intervention descriptions: intervention 1: Undergo 68Ga-PSMA-11 PET/MRI intervention 2: Undergo 68Ga-PSMA-11 PET/MRI intervention 3: Undergo 68Ga-PSMA-11 PET/MRI

Protocol documents:
Prot_SAP_000.pdf: 
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68Ga-PSMA-11 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, Room H-2230 
Stanford, CA 94305 
Phone:  650-725-4711 
Fax:  
 
Email:  aiagaru@stanford.edu  
Co-investigators  
Bruce Daniel, MD, PhD 
  
Stanford, CA 94305  
Phone:  
 
Email:  
  
Pejman Ghanouni, MD, PhD 
 
Stanford, CA 94305  
Phone:  
 
Email:  
  
Geoffrey Sonn, MD 
  
Stanford, CA  94305  
Phone:  
 
Email:  
 
Guido Davidzon, MD 
 
Stanford, CA  94305  
Phone:  
 
Email:   
   
Carina Mari Aparici, MD 
 
Stanford, CA  94305  
Phone:  
 
Email:  
  
 
Biostatistician 
Jarrett Rosenberg, PhD 
 
Stanford, CA 94305 
Phone: 
 
Email:  
  
Study Coordinator  
 
 
  
Protocol IRB-35931  //   PROS0075  //  NCT02678351  
Protocol Amendment 6  //  28 August 2018  
 


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TABLE OF CONTENTS 
SCHEMA ..........................................................................................................................................3 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS .........................................................4 
1. OBJECTIVE ........................................................................................................................................ 5 
2. BACKGROUND .................................................................................................................................. 5 
2.1 Preliminary information .......................................................................................................... 5 
2.2 Study Agent ................................................................................................................................ 9 
2.3 Clinicaltrials.gov ....................................................................................................................... 9 
2.4 Rationale ..................................................................................................................................... 9 
2.5 Study Design ............................................................................................................................ 12 
3. PARTICIPANT SELECTION AND ENROLLMENT PROCEDURES ....................................... 14 
3.1 Inclusion Criteria..................................................................................................................... 14 
3.2 Exclusion Criteria ................................................................................................................... 14 
3.3 Informed Consent Process .................................................................................................. 14 
3.4 Study Timeline ......................................................................................................................... 14 
4. IMAGING AGENT INFORMATION ............................................................................................... 15 
4.1 Study Agent .............................................................................................................................. 15 
4.2 Source of the Study Agent ................................................................................................... 15 
4.3 Ordering .................................................................................................................................... 15 
4.4 Agent Accountability ............................................................................................................. 15 
5. IMAGING SPECIFICS ..................................................................................................................... 15 
5.1 
Modality or Modalities to be used ................................................................................ 15 
5.2 
Details of Imaging (ie, dynamic, static, number of scans, etc) ............................ 15 
5.3 
Image interpretation ........................................................................................................ 16 
6. STUDY PROCEDURES.................................................................................................................. 16 
6.1 
Criteria for Removal from Study .................................................................................. 16 
6.2 
Alternatives ........................................................................................................................ 17 
7. STUDY CALENDAR ........................................................................................................................ 17 
8. ADVERSE EVENTS AND REPORTING PROCEDURES ......................................................... 17 
8.1 Potential Adverse Events ..................................................................................................... 17 
8.2 Adverse Event Reporting ..................................................................................................... 17 
9. REGULATORY CONSIDERATIONS ............................................................................................ 18 
9.1 Institutional Review of Protocol.......................................................................................... 18 
9.2 Data Management Plan ......................................................................................................... 18 
10. 
Statistical Considerations and Evaluation of Results ........................................................ 18 
10.1 Study Endpoints .......................................................................................................................... 18 
10.2 Determination of Sample Size and Accrual Rate ................................................................... 18 
10.2.1 Sample Size and Power Estimate .................................................................................... 18 
10.2.2 Accrual estimates ................................................................................................................ 19 
10.3 Analyses Plans ............................................................................................................................ 19 
10.3.1 Analysis Population ............................................................................................................. 19 
10.3.2 Analysis of Primary Endpoint ............................................................................................. 19 
10.3.3 Analysis of Secondary Endpoints ..................................................................................... 21 
10.3.4 Analysis of Exploratory Endpoints .................................................................................... 23 
10.4 Accrual estimates ........................................................................................................................ 24 
Inclusion/Exclusion Criteria Checklist ............................................................................................... 25 
REFERENCES: ............................................................................................................................... 26 
 


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PROTOCOL SYNOPSIS 
TITLE 
68Ga-PSMA-11 PET/MRI for detection of regional nodal and 
distant metastases in patients with intermediate and high-risk 
prostate cancer 
STUDY PHASE 
Phase 2-3 
INDICATION 
Prostate cancer 
INVESTIGATIONAL PRODUCT  68Ga-PSMA-11;  also known as: 
 
DFKZ-11 
 
HBED-CC PSMA 
 
The “Heidelberg compound” 
SAMPLE SIZE  
200 participants 
PRIMARY OBJECTIVE 
To evaluate 68Ga-PSMA-11 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. 
PRIMARY OBJECTIVE 
Sensitivity, specificity, positive and negative predictive value of 
68Ga-PSMA-11 PET/MRI for the detection of regional nodal 
metastases compared to pathology at radical prostatectomy on a 
per patient basis using nodal regional correlation. 
SECONDARY OBJECTIVES 
Sensitivity, specificity, positive and negative predictive value of 
68Ga-PSMA-11 PET/MRI for the detection of extra-pelvic nodal 
metastases;  visceral metastases; and osseous metastases 
compared to biopsy and imaging follow-up. 
EXPLORATORY ENDPOINTS 
• Sensitivity, specificity, negative and positive predictive value for 
detection of regional nodal metastases in comparison to cross 
sectional imaging performed contemporaneously with the 
PSMA-11 PET. 
• One-year PSA progression-free survival, comparing patients 
with and without pelvic nodal metastases. 
• Correlation between SUVmax from PSMA--11 PET and short 
axis diameter of nodal disease on cross-sectional imaging 
correlate to presence of true pathology. 
• Incidence of osseous and distant metastatic lesions. 
SCHEMA 
 
 
 
 
Eligible participant with prostate cancer 
68Ga-PSMA PET/MRI 


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LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
 
Ga-68; 68Ga 
Gallium-68 
IRB 
Institutional Review Board 
IV 
Intravenous 
MRI 
Magnetic resonance imaging 
NPV 
Negative predictive value  
PPV 
Positive predictive value  
PET 
Positron emission tomography 
SUV 
Standardized Uptake Value 
PSMA 
Prostate Specific Membrane Antigen 
 


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1. OBJECTIVE 
Specific Aim 
To evaluate 68Ga-PSMA-11 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. 
2. BACKGROUND 
2.1 Preliminary information 
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 (1, 2).  
Subsequent treatment is multifaceted and may involve observation, surgery (prostatectomy), 
radiation therapy (external beam or brachytherapy), hormonal therapy, chemotherapy, or a 
combination of these (3-5).  
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 (6). 
Currently, there is controversy regarding the most appropriate imaging modality for accurate 
evaluation of extent of disease.  For instance, MRI can be an effective modality for 
evaluation of the musculoskeletal system, due to much better soft tissue contrast when 
compared to other imaging modalities.  Additionally, the non-invasiveness, lack of ionizing 
radiation and multiplanar imaging capabilities are desirable features of MRI.  Thus, MRI is 
commonly used to detect and evaluate bone and soft tissue tumors.  Whole-body MR 
imaging for the evaluation of metastases compares well with the reference techniques of 
bone scintigraphy and CT.  This imaging modality appears as a practical and acceptable 
alternative especially when extra-osseous metastases are also of concern (7).  Modern MRI 
appears superior to skeletal scintigraphy with respect to sensitivity, specificity, as well as the 
extent of osseous metastasis and provides substantial, therapy-relevant additional 
information.  Current efforts include the introduction of whole-body MRI for detection of 
skeletal metastases.  However, whole-body MRI is a lengthy procedure which many patients 
cannot tolerate, and is also expensive.  
Traditionally, however, 99mTc MDP bone scintigraphy is the method of choice for evaluation 
of osseous metastases, since it allows a whole body survey at a relatively reduced cost and 
because the sensitivity is based not only on the size of the tumor but the response of the 


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bone to the presence of metastasis.  Skeletal scintigraphy is used for initial staging, 
monitoring the response to therapy and detection of areas at risk for pathological fracture.  
Although bone scintigraphy is sensitive for the detection of advanced skeletal metastases, 
early involvement may be missed in some cases in the absence of an osteoblastic response 
as this technique relies on the identification of this response rather than the detection of the 
tumor itself.  Limitations imposed by the spatial resolution of planar scintigraphy and single 
photon emission computed tomography (SPECT) also affect the sensitivity of bone 
scintigraphy in detection of osseous metastases (8).  
While bone scans have a proven role in certain cancers (including prostate and breast), 
within oncology more generally, it is the more recent advent of positron emission 
tomography (PET) that has sparked a renewed interest in molecular imaging because of the 
greater resolution/sensitivity of this modality and also because the radiotracer 18F-FDG has 
proven to be very accurate for imaging a wide variety of malignancies (9,10).  PET imaging 
technology advanced further after the introduction of the combined PET/CT scanner in 2001, 
which allowed merged visualization of functional and anatomical information.  The role of 
18F-FDG PET/CT is proven in a variety of cancers, including lymphoma, colorectal 
carcinoma, lung cancer and melanoma, entities for which it has changed the practice of 
oncology.  However, not all malignant lesions are identified reliably due to variable rates of 
glucose metabolism, contributing to the overall limitations of 18F-FDG PET/CT.  
Indeed, the initial reports and literature reviews suggested a limited role for 18F-FDG 
PET/CT in the evaluation of prostate cancer (11).  In particular, there is convincing evidence 
that for prostate cancer, 18F-FDG PET is less sensitive than bone scintigraphy for the 
detection of skeletal metastases.  But while 18F-FDG PET is limited in the detection of 
osseous metastatic lesions, it may be useful in the detection of metastatic nodal and soft 
tissue disease (12).  The morphology of the metastasis itself appears to be relevant for the 
ability of 18F-FDG PET to detect disease.  PET has been shown to be superior to 
scintigraphy in the detection of lytic metastases because it detects the presence of tumor 
directly by metabolic activity, rather than indirectly by showing tumor involvement due to 
increased bone mineral turnover.  This has allowed the detection of metastatic foci earlier 
with 18F-FDG PET than with bone scintigraphy (13, 14).  This in part explains why the 
recently published results from the National Oncologic PET Registry (NOPR) suggest 
changes in management in one third of the patients with prostate cancer who were 
evaluated with 18F-FDG PET/CT. 
Another way to evaluate the skeleton using PET technology is with 18F sodium fluoride 
(18F-NaF).  In fact, bone scintigraphy with 18F was performed prior to introduction of 99mTc 
based agents, achieving excellent quality studies (15, 16).  18F is an avid bone seeker, a 
property due to the fact that it is an analogue of the hydroxyl group found in the 
hydroxyapatite bone crystals.  18F has the desirable characteristics of high and rapid bone 
uptake accompanied by very rapid blood clearance, which results in a high 
bone-to-background ratio in a short time.  High-quality images of the skeleton can be 
obtained less than an hour after the intravenous administration of 18F.  18F is a positron 
emitter, allowing for PET imaging.  Thus, imaging skeletal lesions with 18F-PET/CT appears 
as a logical approach for acquisition of highly sensitive and specific images.  The lack of 


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reimbursement and the high costs of 18F currently prevent its clinical utilization, but 
18F-PET/CT was proved to be superior in bone lesion detection 99mTc MDP bone scan and 
SPECT in patients with prostate cancer. 
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 (17-19) or metastatic (20) prostate cancer.  Their feasibility in primary 
diagnosis is limited because of uptake in benign tissue such as benign prostatic hyperplasia 
or inflammatory lymph nodes (21, 22). 
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 (23, 24).  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 (25).  However, recent work 
indicates that 18F-FACBC uptake in prostate cancer is similar to that in BPH nodules (26). 
In addition, prostate-specific membrane antigen (PSMA) recently has received increased 
attention (27).  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 (28).  It therefore provides a promising target for prostate 
cancer-specific imaging (29).  Recently methods have been developed to label PSMA 
ligands with 68Ga enabling their use for PET imaging and therapy (30).  Initial experience 
with PET/CT using Glu-NH-CO-NH-Lys-(Ahx)-[68Ga(HBED-CC)] (68Ga-PSMA-11) as a 
68Ga-labelled PSMA ligand suggests that this novel tracer can detect prostate cancer 
relapses and metastases with high contrast by binding to the extracellular domain of PSMA, 
followed by internalization (31).  Improved detection of occult metastatic disease will improve 
treatment efficacy by enabling better patient selection for treatment and prompting more 
extended pelvic node treatment with surgery or radiation for patients with evidence of nodal 
metastases outside the normal lymph node treatment area. 
We conducted a pilot phase evaluation of 68Ga-PSMA-11 under an RDRC-approved 
protocol at Stanford University.  Ten men (age range:  67 to 83 year-old; mean ± SD:  
73.1 ± 5.7) with biochemical recurrence of prostate cancer (PSA range:  2.6-36.4; 
mean ± SD:  12.4 ± 10.6) were enrolled.  PET/CT images were acquired at 51 to 68 minutes 
(mean ± SD:  57.4 ± 6.3) after injection of 3.7 to 4.0 mCi (mean ± SD:  3.8 ± 0.1) of 
68Ga-PSMA.  The uptake of 68Ga-PSMA-11 was identified as described in previously 
published studies referenced above.  
All participants had multiple standard of care imaging studies (CT, MRI, 18F-FDG PET/CT, 
18F-NaF PET/CT, 99mTc MDP bone scan) prior to enrollment that were non-contributory, 
despite rising PSA values.  The participants did not receive treatment in this interval as they 
were managed under a wait and watch strategy due to no identifiable disease.  The interval 


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from biochemical recurrence to the 68Ga-PSMA-11 PET/CT scan ranged 5 to 75 months 
(mean ± SD:  30.8 ± 20.4). 
Biodistribution and localization of 68Ga-PSMA-11 
All participants tolerated the procedure without immediate or delayed (up to 7 days) 
complaints or complications.  The areas with the highest 68Ga-PSMA-11 accumulation are 
the lacrimal grand (mean SUVmax:  9.3 ± 3.3 [range:  4.6 to 14.9] and SUVmean:  5.2 ± 2.3 
[range:  2.5 to 8.8]), the parotid grand (mean SUVmax:  14.2 ± 2.6 [range:  9.9 to 19.1] and 
SUVmean:  11.8 ± 2.6 [range:  7.2 to 16.1]), the submandibular grand (mean SUVmax:  
16.8 ± 3.3 [range:  12.3 to 22.7] and SUVmean:  13.5 ± 2.9 [range:  9.8 to 18.1]), small 
intestine (mean SUVmax:  14.6 ± 4.6 [range:  8.2 to 23.4] and SUVmean:  11.0 ± 3.9 [range:  
5.6 to 18.5]), kidney (mean SUVmax:  35.1 ± 9.9 [range:  14.4 to 46.2] and SUVmean:  
25.8 ± 7.5 [range:  12.0 to 36.0]) and bladder (mean SUVmax:  35.0 ± 24.7 [range:  
9.6 to 78.5] and SUVmean:  26.5 ± 17.4 [range:  7.8 to 67.9]), while moderate uptake was 
noted in the sublingual grand (mean SUVmax:  5.0 ± 2.4 [range:  1.9 to 10.6] and SUVmean:  
3.3 ± 1.6 [range:  1.5 to 7.1]), liver (mean SUVmax:  6.0 ± 1.3 [range:  4.1 to 9.0] and 
SUVmean:  4.1 ± 0.8 [range:  3.2 to 5.7]) and spleen (mean SUVmax:  8.0 ± 3.3 [range:  
2.6 to 12.3] and SUVmean:  6.4 ± 2.7 [range:  2.0 to 10.5]).  Other tissues analyzed had low 
68Ga-PSMA-11 uptake, with SUVmean of less than 1.7.  There were no differences between 
the 68Ga-PSMA-11 biodistribution at 45 minutes post-injection among the 10 participants 
(Figure 2).  The pattern of 68Ga-PSMA-11 uptake is similar to previous reports. 
68Ga-PSMA-11 uptake outside the expected physiologic biodistribution 
There were 45 areas of high 68Ga-PSMA-11 uptake that corresponded on the CT images to 
bone marrow (n = 13), retroperitoneal lymph nodes (n = 12), mediastinal lymph nodes 
(n = 8), pelvic lymph nodes (n = 9), seminal vesicle (n = 2), subclavian lymph node (n = 1).  


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Figure 1:  Maximum intensity projection (MIP) images from 10 participants in the pilot study of 68Ga-PSMA-11 
conducted at Stanford University.  
2.2 Study Agent 
We will use 68Ga-PSMA-11 as the PET radiopharmaceutical.  This agent has previously 
been identified as DFKZ-11;  HBED-CC PSMA;  or the “Heidelberg compound.”  This is not 
an FDA-approved product.  This protocol is submitted to IND 128379. 
2.3 Clinicaltrials.gov  
Since 68Ga-PSMA-11 is not an FDA-approved product, we will register the study on 
clinicaltrials.gov once all approvals will be in place. 
2.4 Rationale 
In this study, we propose to use a well-established PET isotope, Gallium-68 (68Ga), bound 
to a PSMA ligand, (ie, 68Ga-PSMA-11), which has high affinity for prostate specific 
membrane antigen.  68Ga-PSMA-11 has been shown to be superior to other PET tracers 
used in prostate cancer such as 18F-Fluoroethylcholine (FECH) and 
18F-Fluoromethylcholine (32, 33).  Therefore, we propose the following aim: 


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To evaluate 68Ga-PSMA-11 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. 
A prior first-in-human study investigated the biodistribution of 68Ga-PSMA-11 and its ability 
to detect lesions.  Thirty-seven men with prostate cancer underwent whole-body PET/CT 
after an intravenous injection of 68Ga-PSMA-11 (median 121.0 MBq, range 52 to 212 MBq).  
Within healthy organs, kidneys and salivary glands demonstrated the highest radiotracer 
uptake.  Lesions suspicious for PC presented with excellent contrast as early as 1 hour 
post-injection with high detection rates even at low PSA levels (31).  In another study, a total 
of 78 lesions characteristic for prostate cancer were detected in 32 patients using 
68Ga-PSMA-11 PET/CT and 56 lesions were detected in 26 patients using choline PET/CT 
(33).  The higher detection rate in 68Ga-PSMA-11 PET/CT was statistically significant 
(P=0.04).  All lesions detected by 18F-fluoromethylcholine PET/CT were also seen by 
68Ga-PSMA-11 PET/CT.  In conclusion, 68Ga-PSMA-11 PET/CT can detect prostate cancer 
lesions with improved contrast when compared to 18F-fluoromethylcholine PET/CT, 
especially at low PSA levels.  


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Figure 2:  Red arrows point to a nodular pelvic wall metastasis (a, b, histologically-confirmed) and to 
small lymph nodes (c, d) which present with clearly pathological tracer uptake in 68Ga-PSMA-11 
PET/CT (b and d) only.  Yellow arrows point to both catheterized ureters (c, d).  Patient presented 
with a minimal PSA value (0.01 ng/mL) despite visible tumor lesions.  The PSMA-11 ligand is 
therefore able to detect poorly differentiated PC.  a + c Fusion of 18F-fluoromethylcholine PET and 
CT;  b + d fusion of 68Ga-PSMA-11 PET and CT. 
Our initial analysis of the first 33 participants enrolled in the study showed that prostate 
cancer was seen using 68Ga-PSMA-11 PET in all patients, whereas multiparametric MR 
imaging depicted Prostate Imaging Reporting and Data System (PI-RADS) 4 or 5 lesions in 
26 patients and PI-RADS 3 lesions in four patients. Focal uptake was seen in the pelvic 
lymph nodes in five patients. Pathologic examination confirmed prostate cancer in all 
patients, as well as nodal metastasis in three. All patients with normal pelvic nodes in 
PET/MR imaging had no metastases at pathologic examination (34).  


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Figure 3:  74 year-old man (participant #4) with recently diagnosed intermediate risk, T1c, Gleason 
4+4 prostate cancer presenting with PSA of 4.12 ng/mL.  Maximum intensity projection (MIP) PET 
image (A), early transaxial PET (B) and delayed transaxial PET (C) showed focal uptake in 
histopathological proven prostate cancer (F). The milder focal uptake in the left lobe was likewise 
proven to be prostate cancer. Transaxial T2-weighted MRI (D) and DWI (B = 800) MRI (E) are also 
shown. Only the right -side tumor was mpMRI positive (PI-RADS 5). 
2.5 Study Design 
This is a phase 2-3 study with a total of 200 participants with newly-diagnosed intermediate 
or high-risk prostate cancer scheduled to undergo prostatectomy and lymph node 
dissection.  Eligible participants will undergo baseline assessments at enrollment.  Study 
participants will receive 68Ga-PSMA-11 and undergo a PET/MRI.  All patients will first be 
seen by a Stanford Cancer Institute physician (Drs Brooks, Gill, Skinner and Sonn) who will 
refer patients 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 
3 to 7 mCi of 68Ga-PSMA-11 
5. Participant will void immediately prior to the scan 


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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-PSMA-11 PET/MRI may be repeated at the completion of treatment to evaluate 
response to therapy, if requested by the treating physician. 
Objectives of the Study 
Primary 
 
Sensitivity, specificity, positive and negative predictive value of 68Ga-PSMA-11 
PET/MRI for the detection of regional nodal metastases compared to pathology at 
radical prostatectomy on a per patient basis using nodal regional correlation. 
Secondary 
 
Sensitivity, specificity, positive and negative predictive value of 68Ga-PSMA-11 
PET/MRI for the detection of extra-pelvic nodal metastases, visceral metastases and 
osseous metastases compared to biopsy and imaging follow-up. 
Exploratory 
 
Sensitivity, specificity, negative and positive predictive value for detection of regional 
nodal metastases in comparison to cross sectional imaging performed 
contemporaneously with the 68Ga-PSMA-11 PET/MRI PET. 
 
One-year PSA progression free survival, comparing patients with and without pelvic 
nodal metastases. 
 
Correlation between SUVmax from 68Ga-PSMA-11 PET/MRI and short axis diameter 
of nodal disease on cross sectional imaging correlate to presence of true pathology. 
 
Incidence of osseous and distant metastatic lesions. 
Endpoints 
Primary Endpoints 
 
PSMA-11 PET results for regional nodal disease. 
 
Nodal histology results from prostatectomy. 
Secondary endpoints 
 
PSMA-11 PET results for extra-pelvic disease. 


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 
Biopsy results and imaging follow-up results 
Exploratory Endpoints 
 
Time to PSA progression 
 
SUVmax of lesions. 
 
Presence of osseous and distant metastasis.  
 
Safety: blood pressure, heart rate, self reported adverse events 
3. PARTICIPANT SELECTION AND ENROLLMENT PROCEDURES 
3.1 Inclusion Criteria 
 
≥ 18 years-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 90 days of the research PET 
3.2 Exclusion Criteria 
 
Patients not capable of getting PET study due to weight, claustrophobia, or inability 
to lay still for the duration of the exam 
 
Neoadjuvant chemotherapy or radiation therapy prior to prostatectomy, including 
focal ablation techniques (HiFu) 
 
Androgen deprivation therapy or other neoadjuvant treatments prior to PET imaging 
and surgery 
 
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. 


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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-PSMA-11 as the PET radiopharmaceutical.  This agent has previously 
been identified as DFKZ-11;  HBED-CC PSMA;  or the “Heidelberg compound.”  
The administered dosage of 68Ga-PSMA-11 is 111 to 259 MBq (3 to 7 mCi) IV.  We will use 
68Ga-PSMA-11 as the PET radiopharmaceutical. There are 2 publications on dosimetry for 
68Ga-PSMA-11 (PMID: 27260521; 28012435).  The first lists 0.0236 mSv/MBq for the mean 
effective dose, while the other indicates 0.0258 mSv/MBq.  We used the maximum potential 
administered activity of 7 mCi and the higher of the reported dosimetry values.  Therefore, 
259 MBq x 0.0258 mSv/MBq = 6.68 mSv. 
To summarize the results of the published human studies, there were no observed adverse 
events to the radiopharmaceutical.  The measured dosimetry showed that the critical organ 
with 68Ga-PSMA-11 is the spleen, followed by the stomach wall;  pancreas;  and bladder 
wall. The effective dose of 68Ga-PSMA-11 reported (0.0258 mSv/MBq) is similar to 
those of 68Ga-DOTA-TOC (0.023 mSv/MBq), 68Ga-DOTA-NOC (0.025 mSv/MBq), 
68Ga-DOTA-TATE (0.021 mSv/MBq) and 68Ga-NOTA-RGD (0.022 mSv/MBq) (35-38).  
4.2 Source of the Study Agent  
Molecular Imaging Program at Stanford (MIPS) 
Satellite Radiochemistry Facility  
 
Stanford, CA 94305  
4.3 Ordering 
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 (ie, dynamic, static, number of scans, etc) 
A localizer MRI scan will be performed at 45 minutes after injection of 3 to 7 mCi of 
68Ga-PSMA-11 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 


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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).  
5.3 Image interpretation 
1. 68Ga-PSMA-11 PET 
PET images will initially be interpreted  in random order at separate reading sessions by 
3 board-certified nuclear medicine physicians.  Cross-sectional MRI imaging from the PET 
will be available for anatomic correlate.  Final reads for each patient will be interpreted as 
positive or negative for the presence of pelvic nodal disease, and positive or negative for the 
presence of osseous metastatic disease and soft tissue metastases outside of the pelvis.  
Clinical Follow-up 
a. Prostatectomy: patients without evidence of PSMA-11 PET positive nodal or 
metastatic disease noted on imaging will undergo radical prostatectomy.  If a 
PSMA-11 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 PSMA-11 PET without positive nodes on 
pathology, will be rescanned with CT or MRI to determine if the 
suspicious node was thought to be removed.  A PSMA-11 PET may 
be repeated as well at the discretion of the treating physician.  
b. If sites of PSMA-11 PET positive osseous or distant metastatic lesions are 
noted, the urologist will be informed, and further evaluation including further 
imaging (bone scan;  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.  
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.  


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6.2 Alternatives 
The alternative is to not participate in the study.  
7. STUDY CALENDAR 
 
Pre-Study 
Scan Date 
24 to 72 Hours 
Post-Study 
12 Months 
Informed consent 
X 
 
 
 
Demographics 
X 
 
 
 
Medical history 
X 
 
 
 
68Ga-PSMA-11 
 
X 
 
 
Follow-up Call to Participant 
 
 
X 
 
Data analysis 
 
 
 
X 
8. ADVERSE EVENTS AND REPORTING PROCEDURES 
8.1 Potential Adverse Events 
The administration of the radioactive substance will feel like a slight pinprick when given by 
IV 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 68Ga-PSMA-11 PET/MRI.  The 
effective dose from one typical maximum of 259 MBq (range:  3 to 7 mCi) administration of 
68Ga-PSMA-11 is 6.68 mSv.  There is no radiation exposure from MRI.  Therefore, the 
effective dose from one 68Ga-PSMA-11 PET/MRI is 6.68 mSv, approximately equal to 13% 
of the limit that radiation workers (eg, a hospital X-ray technician) are allowed to receive in 
one year.  
8.2 Adverse Event Reporting 
We do not anticipate hazardous situations for the subjects as a result of this protocol.  
However, standard of care procedures will be in place for verification of correct 
radiopharmaceutical dose and route of administration.  The study Principal Investigator (PI) 
or his designee will report all serious adverse events (per 21CFR§312.32) 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 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.  


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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 (eg, 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.  
9.2 Data Management Plan 
The CRFs will be stored in a locked office in the Nuclear Medicine clinic.  Records will be 
kept using OnCore.  
During the clinical investigation, the Protocol Director 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.  Monitoring of the trial will occur every 8 weeks and a 
record of monitoring activities will be maintained by the study team.  
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. Statistical Considerations and Evaluation of Results 
10.1 Study Endpoints 
Primary endpoints:  
 
PSMA-11 PET results for regional nodal disease.  
 
Nodal histology results from prostatectomy.  
These will be expressed as range (mean  SD) of number of lymph nodes identified by PET 
and by dissection during surgery plus histopathology. 
10.2 Determination of Sample Size and Accrual Rate 
10.2.1 Sample Size and Power Estimate 
The estimated sample size will be 200 patients to adequately power the primary aim.  The 
power analysis will be based on the comparison of sensitivity between conventional imaging 
and PSMA-11 PET.  With a power of 80% and a significance level of 0.01, a sample size of 
61 patients with nodal metastases is required.  The following assumptions are made: 
i. 30% of intermediate to high-risk patients have nodal metastases at prostatectomy.  


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ii. 25% of patients will not undergo the planned prostatectomy.  Patients that do not 
undergo prostatectomy will not be included in the analysis population, and will not 
undergo central imaging review.  
iii. Conventional imaging has a 45% detection sensitivity for nodal metastases on a 
per-patient basis (2).  
iv. PSMA-11 PET has a 65% detection sensitivity for nodal metastases on a per-patient 
basis.  
10.2.2 Accrual estimates 
We anticipate enrolling 200 patients in total.  
10.3 Analyses Plans 
10.3.1 Analysis Population 
All patients that undergo prostatectomy and have histology correlates will be included in the 
analysis for the primary endpoint.  
10.3.2 Analysis of Primary Endpoint 
a) Imaging interpretation 68Ga-PSMA-11 PET: 
PET images will be interpreted by 3 different readers in a random order at separate 
reading sessions.  Cross-sectional imaging from the PET will be available for anatomic 
correlate.  Final reads for each patient will be interpreted as positive or negative for the 
presence of pelvic nodal disease, and positive or negative for the presence of osseous 
metastatic disease and soft tissue metastases outside of the pelvis.  
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 1 lesion in 
this region is visually positive.  
i) Lymph nodes will be considered positive if the 68Ga-PSMA-11 uptake is focal and 
greater than adjacent background.  Pelvic lymph nodes will be subclassified 
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-PSMA-11 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-PSMA-11 uptake is focal and 
greater than physiologic bone marrow.  
b) Pathology analysis: 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) Nodes will be marked by location per site-specific protocol.  For example if the 
urologist removed left and right nodal regions separately, then that patient will have 
two nodal regions (left/right).  If a different surgeon removes nodes in six groups 


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(bilateral internal/external/obturator nodes), then that patient will have six nodal 
regions that will be analyzed.  
ii)  Although not routinely performed during standard practice, immunohistochemical 
staining for PSMA-11 of tumor specimens (primary and lymph node metastases) 
may be performed, but is not required for this study.  
iii) The number of nodes counted on pathology will also be recorded.  
c) Analysis plan for Primary Aim 1: For this study to reach success, 2 out of the 3 readers 
will have to demonstrate a detection sensitivity of 65% or greater for nodal metastases.  
Additionally, 2 out of the 3 readers will have to demonstrate a detection specificity of 
90% or greater for regional nodal metastases based upon region as defined below on a 
per patient level.  The sensitivity, specificity, positive and negative predictive value of 
PSMA-11 PET for the detection on a per patient basis will be determined using the 
below criteria: 
i) True positive patient: 
(1) PSMA-11 PET-positive for regional nodes;  pathology at prostatectomy positive 
for regional nodes.  Region will be defined by the granularity used by the 
urologist at time of prostatectomy.  Sensitivity will be calculated at a patient level 
by region, meaning that one correct region would make a true positive on a 
patient level.  Only one node needs to correspond between imaging and 
pathology for a patient to be considered a true positive.  
(2) PSMA-11 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 to 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) PSMA-11 PET-negative for regional nodes;  pathology at prostatectomy negative 
for regional nodes.  
iii) False positive patient: 
(1) PSMA-11 PET-positive for regional nodes;  pathology at prostatectomy is 
negative;  and imaging after prostatectomy demonstrates that node is no longer 
present.  
(2) PSMA-11 PET positive for regional node, but pathology at prostatectomy is 
positive for node but in a different nodal region than that node seen on PSMA-11 
PET.  


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iv) False negative patient: 
(1) PSMA-11 PET negative for regional nodes, but pathology at prostatectomy is 
positive.  
v) Non-evaluable:  
(1) PSMA-11 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.  
10.3.3 Analysis of Secondary Endpoints 
We will report the sensitivity, specificity, positive and negative predictive value of 
PSMA-11 PET over all imaged regions as well as broken down by the following regions: 
extra-pelvic nodal metastases, visceral metastases and osseous metastases.  Follow-up 
for extra-pelvic nodal metastases, visceral metastases and osseous metastases are 
defined as below: 
i) Lymph nodes will be assessed by change in size.  68Ga-PSMA-11 positive lymph 
nodes will be considered: 
(1) True positive:  
- If on follow-up imaging within 3 to 12 months, lymph nodes seen on CT or MRI 
decrease by more than 30% (for patients undergoing systemic treatment of focal 
therapy at this site) or increase by more than 20% in short axis diameter (with a 
minimum of 3 mm in change in size).  
- If patients with solitary lymph node regions show a decrease of PSA by greater 
than 50% after targeted treatment (ie, external beam radiation) and the lymph 
nodes do not change in size (less than 30% decrease or less than 20% increase 
in short axis diameter).  
(2) False positive:  
- If on follow-up imaging within 3 to 12 months, sites of initial 68Ga-PSMA-11 
positive lymph node lesions seen on CT or MRI decrease by more than 30% 
without systemic therapy or focal therapy at this site.  
- If 68Ga-PSMA-11 positive lymph node lesions do not meet the criteria for above 
false positive or true positive findings.  
ii) Visceral lesions (non-lymph node soft tissue or organ) will be assessed by change in 
size.  68Ga-PSMA-11 positive visceral lesions will be considered: 
(1) True positive:  
- If on follow-up imaging within 3 to 12 months, visceral lesions seen on CT or 
MRI decrease by 30% (for patients undergoing systemic treatment of focal 
therapy at this site) or increase by 20% in largest diameter.  


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- If patients with solitary visceral metastasis show a decrease of PSA by greater 
than 50% after targeted treatment (ie, external beam radiation) and lesions do 
not change in size (less than 30% decrease or 20% increase in largest diameter).  
(2) False positive:  
- If on follow-up imaging within 3 to 12 months, sites of initial 68Ga-PSMA-11 
positive visceral lesions seen on CT or MRI decrease by more than 30% without 
systemic therapy or focal therapy at this site.  
- If 68Ga-PSMA-11 positive visceral lesions do not meet the criteria for above 
false positive or true positive findings.  
iii) 68Ga-PSMA-11 positive bone lesions will be considered: 
(1) True positive: 
- If there was a corresponding positive sclerotic lesion on the CT portion of the 
68Ga-PSMA-11 PET.  
- If there is focal uptake seen on the baseline bone scan performed within one 
month of 68Ga-PSMA-11 PET.  
- If there is a lesion noted on the initial MRI performed within one month of 
68Ga-PSMA-11 PET.  
- If within 12 months, follow-up CT demonstrates development of sclerosis.  
- If within 12 months, follow-up MRI demonstrates a new bone lesion.  
- If within 12 months, follow-up bone scan demonstrates new focal uptake.  
(2) False positive: 
- If 68Ga-PSMA-11 positive bone lesions do not meet the criteria for true positive 
findings.  
iv) Histopathology correlation: for lesions that have biopsy correlation, we will use the 
following criteria to determine positive and negative lesions: 
(1) Positive HP/Biopsy: Confirmed sites of metastatic or tumor involvement by 
histopathology/biopsy will be discussed with the responsible physician/surgeon.  
(2) Negative Biopsy: Patients with suspected tumor recurrence on 68Ga-PSMA-11 
PET with negative histopathology/biopsy will be handled as outlined below: 
(a) Lymph nodes: 
 
For patients undergoing nodal dissection: Patients will be rescanned with 
dedicated CT or MRI to determine if the suspicious 
68Ga-PSMA-11-positive node was removed.  
- If 68Ga-PSMA-11 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.    


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- If the corresponding node was removed, then this will be considered a 
False Positive.  
 
For patients undergoing needle biopsy: Images of the procedure will be 
reviewed to determine if the correct node was biopsied.  
- If the correct node was biopsied, then a negative biopsy will be 
considered a False Positive.  
- If the incorrect node was biopsied, then follow-up imaging as described 
above will be performed.  
(b) Bone lesions:  Given the high rate of false negative biopsies for osseous 
metastases in patients with prostate cancer, patients with negative bone 
biopsies of 68Ga-PSMA-11 PET-positive lesions will be further evaluated: 
 
If pathology demonstrates an alternative diagnoses that is known to be 
68Ga-PSMA-11-positive (eg, renal cell carcinoma (RCC) metastases;  
Paget’s disease), then this will be considered a False Positive.  
 
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.  
(c) Additionally a repeat 68Ga-PSMA-11 can also be obtained, as allowable, in 
addition to repeat conventional imaging (CT and/or MRI) in cases of negative 
biopsy to determine if the biopsy was true negative or false negative.  
10.3.4 Analysis of Exploratory Endpoints 
PPVs on a per-patient and per-region-basis of 68Ga-PSMA-11 PET for detection of tumor 
location confirmed by histopathology/biopsy and conventional imaging follow-up will be 
calculated and reported along with the corresponding two-sided 95% confidence intervals. 
The paired McNemar’s test will be used to compare the PPVs of 68Ga-PSMA-11 PET 
imaging to the PPVs of conventional imaging.  
Sensitivity, specificity, and NPVs on a per-patient basis of 68Ga-PSMA-11 PET for detection 
of tumor location confirmed by histopathology/biopsy will be summarized in tabular format. 
Furthermore, the positive and negative likelihood ratios (LR+ and LR-) will be calculated and 
reported.  95 confidence intervals of sensitivity, specificity, and NPV will be calculated using 
the Wilson score method. The comparisons of sensitivity, specificity, and NPV on a 
per-patient basis of 68Ga-PSMA-11 PET imaging will be compared to of sensitivity, 
specificity, and NPV on a per-patient basis of conventional imaging using a paired 
McNemar’s test.  
Detection rates on a per-patient basis of 68Ga-PSMA-11 PET stratified by PSA value 
(0.2 to < 0.5;  0.5 to < 1.0;  1.0 to < 2.0;  2.0 to < 5.0;  ≥ 5.0) will be summarized in tabular 
format and compared between PSA strata using chi-square analysis. The impact of 
68Ga-PSMA-11 PET on clinical management in BCR patients will be evaluated using 
descriptive statistics.  


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10.4 Accrual estimates 
We expect the accrual of 40 patients each year for 5 years.  There are approximately 
120 radical prostatectomies performed on patients with newly diagnosed prostate cancer at 
Stanford each year.  We plan to enroll 40 participants/year and this is achievable given our 
experience with other protocols and the support from the referring physicians, Drs Chung, 
Sonn, Brooks, and Gill.  
 


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Inclusion/Exclusion Criteria Checklist  
Protocol Title: 
68Ga-PSMA-11 PET/MRI for detection of regional nodal and distant 
metastases in patients with intermediate and high-risk prostate cancer 
Protocol Number: 
IRB-35931  /  PROS0075 
Principal Investigator: 
Andrei Iagaru, MD 
 
Inclusion Criteria – Yes must be checked to be eligible 
(From IRB approved protocol) 
Yes 
No 
Supporting 
Documentation 
1. ≥ 18 years-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 of the 
research 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.  
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: 
 
Exclusion Criteria –No must be checked to be eligible 
(From IRB approved protocol) 
Yes 
No 
Supporting 
Documentation 
1. 
Patients not capable of getting PET study due to weight, 
claustrophobia, or inability to lay still for the duration of 
the exam 
☐ 
☐ 
☐ 
2. 
Neoadjuvant chemotherapy or radiation therapy prior to 
prostatectomy including focal ablation techniques (HiFu) 
☐ 
☐ 
☐ 
3. 
Androgen deprivation therapy or other neoadjuvant 
treatments prior to PET imaging surgery 
☐ 
☐ 
☐ 
4. 
Metallic implants (contraindicated for MRI) 
☐ 
☐ 
☐ 
Secondary Reviewer Signature: 
Date: 
Printed Name: 


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REFERENCES: 
 
1. 
Smith RA, Cokkinides V, Brawley OW. Cancer screening in the United States, 2009: a 
review of current American Cancer Society guidelines and issues in cancer screening. CA 
Cancer J Clin. 2009;59(1):27-41. 
2. 
Lacy GL, 2nd, Soderdahl DW, Hernandez J. Optimal cost-effective staging evaluations 
in prostate cancer. Curr Urol Rep. 2007;8(3):190-6. 
3. 
Roscigno M, Sangalli M, Mazzoccoli B, Scattoni V, Da Pozzo L, Rigatti P. Medical 
therapy of prostate cancer. A review. Minerva Urol Nefrol. 2005;57(2):71-84. 
4. 
Oh WK, Kantoff PW. Treatment of locally advanced prostate cancer: is chemotherapy 
the next step? Journal of clinical oncology. 1999;17(11):3664-75. 
5. 
Jani AB. Management strategies for locally advanced prostate cancer. Drugs Aging. 
2006;23(2):119-29. 
6. 
Lund F, Smith PH, Suciu S. Do bone scans predict prognosis in prostatic cancer? A 
report of the EORTC protocol 30762. British journal of urology. 1984;56(1):58-63. 
7. 
Chan Y, Chan K, Lam W, Metreweli C. Comparison of whole body MRI and radioisotope 
bone scintigram for skeletal metastases detection. Chin Med J (Engl). 1997;110(6):485-9. 
8. 
Even-Sapir E. Imaging of malignant bone involvement by morphologic, scintigraphic, and 
hybrid modalities. J Nucl Med. 2005;46(8):1356-67. 
9. 
Strauss LG, Conti PS. The applications of PET in clinical oncology. J Nucl Med. 
1991;32(4):623-48; discussion 49-50. 
10. 
Fletcher JW, Djulbegovic B, Soares HP, et al. Recommendations on the use of 18F-FDG 
PET in oncology. The Journal of nuclear medicine. 2008;49(3):480-508. 
11. 
Gambhir SS, Czernin J, Schwimmer J, Silverman DH, Coleman RE, Phelps ME. A 
tabulated summary of the FDG PET literature. J Nucl Med. 2001;42(5 Suppl):1S-93S. 
12. 
Jadvar H, Pinski JK, Conti PS. FDG PET in suspected recurrent and metastatic prostate 
cancer. Oncol Rep. 2003;10(5):1485-8. 
13. 
Peterson JJ, Kransdorf MJ, O'Connor MI. Diagnosis of occult bone metastases: positron 
emission tomography. Clin Orthop Relat Res. 2003(415 Suppl):S120-8. 
14. 
Bohdiewicz PJ, Wong C-YO, Kondas D, Gaskill M, Dworkin HJ. High predictive value of 
F-18 FDG PET patterns of the spine for metastases or benign lesions with good agreement 
between readers. Clinical nuclear medicine. 2003;28(12):966-70. 
15. 
Shirazi PH, Rayudu GV, Fordham EW. 18F bone scanning: review of indications and 
results of 1,500 scans. Radiology. 1974;112(2):361-8. 
16. 
Grant FD, Fahey FH, Packard AB, Davis RT, Alavi A, Treves ST. Skeletal PET with 


IRB-35931 
Page 27 of 28 
CONFIDENTIAL 
SRC Amendment 6;  28 August 2018  
18F-fluoride: applying new technology to an old tracer. J Nucl Med. 2008;49(1):68-78. 
17. 
Sandblom G, Sorensen J, Lundin N, Haggman M, Malmstrom PU. Positron emission 
tomography with C11-acetate for tumor detection and localization in patients with 
prostate-specific antigen relapse after radical prostatectomy. Urology. 2006;67(5):996-1000. 
18. 
Oyama N, Miller TR, Dehdashti F, et al. 11C-Acetate PET Imaging of Prostate Cancer: 
Detection of Recurrent Disease at PSA Relapse. Journal of Nuclear Medicine. 
2003;44(4):549-55. 
19. 
Wachter S, Tomek S, Kurtaran A, et al. 11C-acetate positron emission tomography 
imaging and image fusion with computed tomography and magnetic resonance imaging in 
patients with recurrent prostate cancer. J Clin Oncol. 2006;24(16):2513-9. 
20. 
Kotzerke J, Volkmer BG, Glatting G, et al. Intraindividual comparison of [11C]acetate 
and [11C]choline PET for detection of metastases of prostate cancer. Nuklearmedizin. 
2003;42(1):25-30. 
21. 
Souvatzoglou M, Weirich G, Schwarzenboeck S, et al. The sensitivity of [11C]choline 
PET/CT to localize prostate cancer depends on the tumor configuration. Clin Cancer Res. 
2011;17(11):3751-9. 
22. 
Rietbergen DD, van der Hiel B, Vogel W, Stokkel MP. Mediastinal lymph node uptake in 
patients with prostate carcinoma on F18-choline PET/CT. Nucl Med Commun. 
2011;32(12):1143-7. 
23. 
Heinisch M, Dirisamer A, Loidl W, et al. Positron emission tomography/computed 
tomography with F-18-fluorocholine for restaging of prostate cancer patients: meaningful at PSA 
< 5 ng/mL? 
24. 
Vees H, Buchegger F, Albrecht S, et al. 18F-choline and/or 11C-acetate positron 
emission tomography: detection of residual or progressive subclinical disease at very low 
prostate-specific antigen values (<1 ng/mL) after radical prostatectomy. 
25. 
Nanni C, Schiavina R, Boschi S, et al. Comparison of 18F-FACBC and 11C-choline 
PET/CT in patients with radically treated prostate cancer and biochemical relapse: preliminary 
results. Eur J Nucl Med Mol Imaging. 2013;40 Suppl 1:S11-7. 
26. 
Turkbey B, Mena E, Shih J, et al. Localized prostate cancer detection with 18F FACBC 
PET/CT: comparison with MR imaging and histopathologic analysis. Radiology. 
2014;270(3):849-56. 
27. 
Schäfer M, Bauder Wüst U, Leotta K, et al. A dimerized urea-based inhibitor of the 
prostate-specific membrane antigen for 68Ga-PET imaging of prostate cancer. 
28. 
Sweat SD, Pacelli A, Murphy GP, Bostwick DG. Prostate-specific membrane antigen 
expression is greatest in prostate adenocarcinoma and lymph node metastases. 


IRB-35931 
Page 28 of 28 
CONFIDENTIAL 
SRC Amendment 6;  28 August 2018  
29. 
Eder M, Eisenhut M, Babich J, Haberkorn U. PSMA as a target for radiolabelled small 
molecules. 
30. 
Hillier SM, Maresca KP, Femia FJ, et al. Preclinical evaluation of novel 
glutamate-urea-lysine analogues that target prostate-specific membrane antigen as molecular 
imaging pharmaceuticals for prostate cancer. Cancer Res. 2009;69(17):6932-40. 
31. 
Afshar Oromieh A, Malcher A, Eder M, et al. PET imaging with a [68Ga]gallium-labelled 
PSMA ligand for the diagnosis of prostate cancer: biodistribution in humans and first evaluation 
of tumour lesions. 
32. 
Afshar Oromieh A, Haberkorn U, Eder M, Eisenhut M, Zechmann CM. 
[68Ga]Gallium-labelled PSMA ligand as superior PET tracer for the diagnosis of prostate 
cancer: comparison with 18F-FECH. 
33. 
Afshar Oromieh A, Zechmann C, Malcher A, et al. Comparison of PET imaging with a 
(68)Ga-labelled PSMA ligand and (18)F-choline-based PET/CT for the diagnosis of recurrent 
prostate cancer. 
34. 
Park SY, Zacharias C, Harrison C, et al. Gallium 68PSMA-11 PET/MR Imaging in 
Patients with Intermediate- or High-Risk Prostate Cancer. Radiology;0(0):172232. 
35. 
Hartmann H, Zophel K, Freudenberg R, et al. [Radiation exposure of patients during 
68Ga-DOTATOC PET/CT examinations]. Nuklearmedizin. 2009;48(5):201-7. 
36. 
Pettinato C, Sarnelli A, Di Donna M, et al. 68Ga-DOTANOC: biodistribution and 
dosimetry in patients affected by neuroendocrine tumors. Eur J Nucl Med Mol Imaging. 
2008;35(1):72-9. 
37. 
Sandström M, Velikyan I, Garske-Román U, et al. Comparative Biodistribution and 
Radiation Dosimetry of 68Ga-DOTATOC and 68Ga-DOTATATE in Patients with 
Neuroendocrine Tumors. The Journal of nuclear medicine. 2013;54(10):1755-9. 
38. 
Kim JH, Lee JS, Kang KW, et al. Whole-body distribution and radiation dosimetry of 
(68)Ga-NOTA-RGD, a positron emission tomography agent for angiogenesis imaging. Cancer 
Biother Radiopharm. 2012;27(1):65-71. 

ICF_001.pdf: 
 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Andrei Iagaru, M.D. 
Protocol Title:    
68Ga- PSMA PET/MRI for detection of regional nodal and distant metastases in patients with 
intermediate and high-risk prostate cancer 
 
 
 
      
 
 
 
                          Page 1 of 14 
 
Participant ID: 
IRB Use Only 
Approval Date:   December 1, 2020 
Expiration Date:  December 1, 2021 
68Ga- PSMA PET/MRI for detection of regional nodal and distant 
metastases in patients with intermediate and high-risk prostate cancer 
 
 
Are you participating in any other research studies? _____ Yes _____No 
PURPOSE OF RESEARCH  
 
You are invited to participate in a research study of an experimental drug. You were selected as a 
possible subject in this study because you have been diagnosed with prostate cancer. The purpose of 
this research study is to see if your tumor can be identified using a special procedure called a positron 
emission tomography (PET) scan. PET/MRI is used to describe information regarding the function, as 
well as location and size of a tumor. You will first have a localizer MRI, followed by an injection with 
a radioactive drug called 68Ga-PSMA that binds to tumor cells that have specific receptors and then 
have a PET scan. We believe this special PET/MRI scan will be able to see smaller tumors than the 
standard of care contrast-enhanced CT or MRI scan. 68Ga-PSMA is considered investigational in the 
US, which means that it has not been approved by the U.S. Food and Drug Administration (FDA).  
VOLUNTARY PARTICIPATION 
Your participation in this study is entirely voluntary.  Your decision not to participate will not 
have any negative effect on you or your medical care.  You can decide to participate now, but 
withdraw your consent later and stop being in the study without any loss of benefits or medical 
care to which you are entitled. 
 
If you decide to terminate your participation in this study, you should notify 
.   
 
This research study is looking for people diagnosed with prostate cancer that are suspected to have 
recurrent disease. Stanford University expects to enroll 200 research study participants over 5 years. 
DURATION OF STUDY INVOLVEMENT  
If you agree to take part in this study, your involvement will include 1 visit (up to 3 hours). 
The PET/MRI scan will require that you spend up to 3 hours in the Lucas Center for Imaging.  
PROCEDURES 
If you choose to participate, Dr. Andrei Iagaru and his research study staff will require the following: 
1. After signed the informed consent document, participants will be given a copy of the signed 
form. 


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Andrei Iagaru, M.D. 
Protocol Title:    
68Ga- PSMA PET/MRI for detection of regional nodal and distant metastases in patients with 
intermediate and high-risk prostate cancer 
 
 
 
      
 
 
 
                          Page 2 of 14 
 
Participant ID: 
IRB Use Only 
Approval Date:   December 1, 2020 
Expiration Date:  December 1, 2021 
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 3 to 7 mCi of 
68Ga-PSMA-11 
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. 
You will be asked to lie very still during the scan because movement can interfere with the results. 
You will be asked to breath normally during the scan. During the scan, you might hear a humming 
noise but you will not feel anything unusual. You may feel the table move while images are being 
taken at certain locations on your body. Our technologist will monitor you during the exam. 
The MRI scanning procedure is very much like an x-ray CT scan.  You may be given an IV 
(intravenous) contrast injection to enhance the results of your study. If you have had a previous 
reaction to Gadolinium-based contrast agents or a history of severe allergies, please notify the 
operator/investigator. If you have kidney problems, please tell the operator. You will be asked to lie on 
a long narrow couch for about 45-60 minutes while the machine gathers data.   
During this time, you will not be exposed to x-rays, but rather a strong magnetic field and 
radiofrequency magnetic fields. You will not feel either. You will, however, hear repetitive tapping 
noises that arise from the MR scanner. We will provide earplugs or headphones that you will be 
required to wear. The space within the large magnet in which you lie is somewhat confined, although 
we have taken many steps to relieve the "claustrophobic" feeling. 
Your test results will be maintained as part of your Stanford medical record. If you do not have a 
Stanford medical record, one will be created during this research study. 
If your partner is able to become pregnant, you and your partner must use adequate contraception while 
you are participating in the study. Your doctor will discuss with you what methods of birth control are 
considered adequate. You should inform your study doctor if your partner becomes pregnant. 


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Andrei Iagaru, M.D. 
Protocol Title:    
68Ga- PSMA PET/MRI for detection of regional nodal and distant metastases in patients with 
intermediate and high-risk prostate cancer 
 
 
 
      
 
 
 
                          Page 3 of 14 
 
Participant ID: 
IRB Use Only 
Approval Date:   December 1, 2020 
Expiration Date:  December 1, 2021 
PARTICIPANT RESPONSIBILITIES           
 
As a participant, your responsibilities include:  
 Follow the instructions of the Protocol Director and study staff. 
 Keep your study appointments.  If it is necessary to miss an appointment, please contact the 
Protocol Director or research study staff to reschedule as soon as you know you will miss the 
appointment. 
 Tell the Protocol Director or research study staff about any side effects, doctor visits, or 
hospitalizations that you may have. 
 Tell the Protocol Director or research staff if you believe you might be pregnant or gotten 
your partner pregnant. 
 Ask questions as you think of them. 
 Tell the Protocol Director or research staff if you change your mind about staying in the 
study. 
 
WITHDRAWAL FROM STUDY 
 
If you first agree to participate and then you change your mind, you are free to withdraw your 
consent and discontinue your participation at any time. Your decision will not affect your ability 
to receive medical care for your disease and you will not lose any benefits to which you would 
otherwise be entitled.  
 
If you withdraw from the study, please contact the study staff to let them know of your decision. 
You will receive a follow up phone call to ask if you had any adverse effects from your 
participation in the study. 
 
If you decided to withdraw from the study after the tracer is injected and before the scan is done, 
we would like to observe you for any adverse reaction for up to an hour. Once the IVs have been 
removed, it will be safe for you to leave. 
 
The Protocol Director may also withdraw you from the study without your consent for one or 
more of the following reasons: 
 Failure to follow the instructions of the Protocol Director and study staff. 
 The Protocol Director decides that continuing your participation could be harmful to you. 
 Pregnancy. 
 You need treatment not allowed in the study. 
 The study is cancelled.  
 Other administrative reasons. 
 Unanticipated circumstances. 
 
 


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Andrei Iagaru, M.D. 
Protocol Title:    
68Ga- PSMA PET/MRI for detection of regional nodal and distant metastases in patients with 
intermediate and high-risk prostate cancer 
 
 
 
      
 
 
 
                          Page 4 of 14 
 
Participant ID: 
IRB Use Only 
Approval Date:   December 1, 2020 
Expiration Date:  December 1, 2021 
PET/MRI FOR FUTURE RESEARCH  
We would like to save the images and data from your PET/MRI scans for future research projects.  
You have the right to refuse to allow us the use of your data for future research. You may withdraw 
from this study at any time. If you decide later to withdraw from the study, the PHI obtained up until 
that withdrawal might be used in the study. 
Any images that are used in research may result in new products, tests, or discoveries.  In some 
instances, these may have potential commercial value and may be developed and owned by the 
Investigators, Stanford University and/or others. However, participants in the study do not retain any 
property rights to the materials. Therefore, you would not share in any financial benefits from these 
products, tests, or discoveries. 
Do you agree to allow us to store your data for future research?  
 Yes 
No   
Please initial _______________ 
POSSIBLE RISKS, DISCOMFORTS, AND INCONVENIENCES  
There are risks, discomforts, and inconveniences associated with any research study. These 
deserve careful thought. You should talk with the Protocol Director if you have any questions. 
Risks, discomfort and inconveniences include: 
 Time involved for the visits to the hospital 
 Bruising at the venipuncture/IV site for the radiopharmaceutical injection 
 
PET related risks: 
This research study involves exposure to radiation from one 68Ga-PSMA PET/MRI. The 
effective dose from one typical maximum of 259 MBq (range: 3-7 mCi) administration of 68Ga-
PSMA is 6.68 mSv. There is no radiation exposure from MRI. Therefore, the effective dose 
from one 68Ga-PSMA PET/MRI is 6.68 mSv, approximately equal to 13% of the limit that 
radiation workers (for example, a hospital x-ray technician) are allowed to receive in one year. 
This amount of radiation involves minimal risk and is necessary to obtain the research 
information desired.   
 
Reasonably foreseeable risks include: 
 Physical risks – from study medications and procedures (e.g., venipuncture, exposure 
to radiation. 
 This procedure may involve risks to you that are currently unforeseeable. 
 
 


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Andrei Iagaru, M.D. 
Protocol Title:    
68Ga- PSMA PET/MRI for detection of regional nodal and distant metastases in patients with 
intermediate and high-risk prostate cancer 
 
 
 
      
 
 
 
                          Page 5 of 14 
 
Participant ID: 
IRB Use Only 
Approval Date:   December 1, 2020 
Expiration Date:  December 1, 2021 
MRI (MAGNETIC RESONANCE IMAGING) 
This MRI machine uses a strong magnet and radiofrequency magnetic fields to make images of the 
body interior.  
RISKS of MRI: 
Magnetic fields do not cause harmful effects at the levels used in the MRI machine. However, the MR 
scanner uses a very strong magnet that will attract some metals and affect some electronic devices.   
If you have a cardiac pacemaker or any other biomedical device in or on your body, it is very 
important that you tell the operator/investigator immediately.   
As metallic objects may experience a strong attraction to the magnet, it is also very important that you 
notify the operator of any metal objects (especially surgical clips), devices, or implants that are in or on 
your body before entering the magnet room.  All such objects must be removed (if possible) before 
entering the magnet room.  In some cases, having those devices means you should not have an MRI 
scan performed.  In addition, watches and credit cards should also be removed as these could be 
damaged. You will be provided a way to secure these items.   
If you have any history of head or eye injury involving metal fragments, if you have ever worked in a 
metal shop, or if you could be pregnant, you should notify the operator/investigator. 
You should also notify the operator/investigator if you have any tattoos on your body, including 
eyeliner and other permanent makeup.  Tattoos could become warm and irritated during the scan and 
remain so for several days.  If you would prefer not to participate in the MR scan due to the presence 
of tattoos on your body, please inform a research team member. 
There is a possibility that you will experience a localized twitching sensation due to the magnetic field 
changes during the scan. This is expected and should not be painful.  
If you have had a previous reaction to Gadolinium-based contrast agents, a history of severe allergies, 
or a history of kidney disease, please notify the operator/investigator.   
Some of the hardware, imaging software and devices being used in your scan are not approved by the 
FDA, but are similar to counterparts that have been approved by the FDA. There is a small risk of 
heating from the cables associated with these devices.  Please report any heating sensation 
immediately.   
IF YOU FEEL DISCOMFORT AT ANY TIME, NOTIFY THE OPERATOR AND YOU CAN 
DISCONTINUE THE EXAM AT ANYTIME. 
The scans performed in this study are for specific research purposes and are not optimized to find 
medical abnormalities.  The investigators for this project may not be trained to perform medical 


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Andrei Iagaru, M.D. 
Protocol Title:    
68Ga- PSMA PET/MRI for detection of regional nodal and distant metastases in patients with 
intermediate and high-risk prostate cancer 
 
 
 
      
 
 
 
                          Page 6 of 14 
 
Participant ID: 
IRB Use Only 
Approval Date:   December 1, 2020 
Expiration Date:  December 1, 2021 
diagnosis. The investigators and Stanford are not responsible for failure to find existing abnormalities 
with these MRI scans. However, on occasion the investigator may notice a finding on an MRI scan that 
seems abnormal. When this occurs, a physician will be consulted as to whether the findings merit 
further investigation, in which case the investigator will contact you and your primary care physician 
and inform you of the finding. The decision as to whether to proceed with further examination or 
treatment lies solely with you and your physician. The investigators, the consulting physician, and 
Stanford are not responsible for any examination or treatment that you undertake based on these 
findings. Because the images collected in this study may not comprise a proper clinical MRI scan, 
these images will not be made available for diagnostic purposes. 
Dizziness and nausea may occur if the head is moved rapidly within the bore of the magnet. 
POTENTIAL BENEFITS 
We don’t know if you will benefit from being in this study. We may be able to see more cancer lesions 
compared to other scans. 
 
We hope that in the future others will benefit from this study because of knowledge gained in 
determining whether 68Ga-PSMA PET/MRI scans are more sensitive than the current standard of care 
scans for detecting prostate cancer. 
WE CANNOT AND DO NOT GUARANTEE OR PROMISE THAT YOU WILL RECEIVE 
ANY BENEFITS FROM THIS STUDY. 
ALTERNATIVES 
The alternative is to not participate in this study. 
PARTICIPANT’S RIGHTS 
You should not feel obligated to agree to participate. Your questions should be answered clearly and to 
your satisfaction.  
If you decide not to participate, tell the Protocol Director. You will still receive care for your disease 
and will not lose any benefits to which you would otherwise be entitled.  
You will be told of any important new information that is learned during the course of this research 
study, which might affect your condition or your willingness to continue participation in this study. 
 
 


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Andrei Iagaru, M.D. 
Protocol Title:    
68Ga- PSMA PET/MRI for detection of regional nodal and distant metastases in patients with 
intermediate and high-risk prostate cancer 
 
 
 
      
 
 
 
                          Page 7 of 14 
 
Participant ID: 
IRB Use Only 
Approval Date:   December 1, 2020 
Expiration Date:  December 1, 2021 
CONFIDENTIALITY 
The results of this research study may be presented at scientific or medical meetings or published in 
scientific journals.  Your identity and/or your personal health information will not be disclosed except 
as authorized by you or as required by law.  However, there is always some risk that even de-identified 
information might be re-identified.  
Patient information may be provided to Federal and other regulatory agencies as required.  The Food 
and Drug Administration (FDA), for example, may inspect research records and learn your identity if 
this study falls within its jurisdiction. 
The purpose of this research study is to obtain data or information on the safety and effectiveness of 
68Ga-PSMA; the results may be provided to the Food and Drug Administration, as well as to the 
Society of Nuclear Medicine and Molecular Imaging (SNMMI) and GE Healthcare. 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by 
U.S. Law.  This Web site will not include information that can identify you.  At most, the Web site will 
include a summary of the results.  You can search this Web site at any time. 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Andrei Iagaru, M.D. 
Protocol Title:    
68Ga- PSMA PET/MRI for detection of regional nodal and distant metastases in patients with 
intermediate and high-risk prostate cancer 
 
 
 
      
 
 
 
                          Page 8 of 14 
 
Participant ID: 
IRB Use Only 
Approval Date:   December 1, 2020 
Expiration Date:  December 1, 2021 
USE AND DISCLOSURE OF PROTECTED HEALTH INFORMATION 
Authorization To Use Your Health Information For Research Purposes  
Because information about you and your health is personal and private, it generally 
cannot be used in this research study without your written authorization. If you sign this 
form, it will provide that authorization. The form is intended to inform you about how 
your health information will be used or disclosed in the study. Your information will 
only be used in accordance with this authorization form and the informed consent form 
and as required or allowed by law. Please read it carefully before signing it.   
What is the purpose of this research study and how will my health information be 
utilized in the study? 
This study will attempt to correlate the results of standard of care scans with 68Ga-
PSMA PET/MRI scan, in order to determine the best approach for evaluation of extent 
of prostate cancer. Your health information related to this study, including but not 
limited to your medical history, lab results, and imaging results, may be used to 
correlate with the PET/MRI results. Your health information may be used in scientific 
publications, but your identity will not be disclosed. 
 
Do I have to sign this authorization form? 
You do not have to sign this authorization form. But if you do not, you will not be able 
to participate in this research study. Signing the form is not a condition for receiving 
any medical care outside the study. 
 
If I sign, can I revoke it or withdraw from the research later? 
If you decide to participate, you are free to withdraw your authorization regarding the 
use and disclosure of your health information (and to discontinue any other participation 
in the study) at any time. After any revocation, your health information will no longer 
be used or disclosed in the study, except to the extent that the law allows us to continue 
using your information (e.g., necessary to maintain integrity of research). If you wish to 
revoke your authorization for the research use or disclosure of your health information 
in this study, you must write to Dr. Andrei Iagaru, 300 Pasteur Drive H2200, MC 5281, 
Stanford, CA 94305. 
 
What Personal Information Will Be Used or Disclosed? 
Your health information related to this study may be used or disclosed in connection 
with this research study, including, but not limited to, your name, medical record 


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Andrei Iagaru, M.D. 
Protocol Title:    
68Ga- PSMA PET/MRI for detection of regional nodal and distant metastases in patients with 
intermediate and high-risk prostate cancer 
 
 
 
      
 
 
 
                          Page 9 of 14 
 
Participant ID: 
IRB Use Only 
Approval Date:   December 1, 2020 
Expiration Date:  December 1, 2021 
number, medical history, sex, age, diagnosis, results of scans and pathology review, 
physical examination, lab tests, and imaging tests such as x-rays, CT scans, MRI scans, 
bone scans, and ultrasounds studies.  
 
Who May Use or Disclose the Information? 
The following parties are authorized to use and/or disclose your health information in 
connection with this research study: 
 Dr. Andrei Iagaru (the Protocol Director) and members of the research team 
including technicians and research coordinators 
 The Stanford University Administrative Panel on Human Subjects in Medical 
Research and any other unit of Stanford University as necessary 
 
Who May Receive / Use the Information? 
The parties listed in the preceding paragraph may disclose your health information to 
the following persons and organizations for their use in connection with this research 
study: 
 The Office for Human Research Protections in the U.S. Department of Health and 
Human Services 
 The Food and Drug Administration (FDA) 
 SNMMI 
 GE Healthcare 
Your information may be re-disclosed by the recipients described above, if they are not 
required by law to protect the privacy of the information. 
 
When will my authorization expire? 
Your authorization for the use and/or disclosure of your health information will expire 
December 31, 2050. 
 
 
 
 
 
 
 
 


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Andrei Iagaru, M.D. 
Protocol Title:    
68Ga- PSMA PET/MRI for detection of regional nodal and distant metastases in patients with 
intermediate and high-risk prostate cancer 
 
 
 
      
 
 
 
                          Page 10 of 14 
 
Participant ID: 
IRB Use Only 
Approval Date:   December 1, 2020 
Expiration Date:  December 1, 2021 
 
 
______________________________             
   
 
______________ 
Signature of Adult Participant                                         
 
Date 
 
 
________________________________             
 
Print Name of Adult Participant                                         
 
 
 
_______________________________                        
 
______________ 
Signature of Legally Authorized Representative (LAR)     
Date 
(e.g., parent, guardian or conservator) 
 
 
________________________________             
 
Print Name of LAR                                         
 
 
________________________________________________________ 
LAR’s Authority to Act for Participant 
(e.g., parent, guardian or conservator) 


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Andrei Iagaru, M.D. 
Protocol Title:    
68Ga- PSMA PET/MRI for detection of regional nodal and distant metastases in patients with 
intermediate and high-risk prostate cancer 
 
 
 
      
 
 
 
                          Page 11 of 14 
 
Participant ID: 
IRB Use Only 
Approval Date:   December 1, 2020 
Expiration Date:  December 1, 2021 
FINANCIAL CONSIDERATIONS 
PAYMENT: You will be paid $150 for being in this research study after completion of PET MRI 
scan. 
 
Payments may only be made to U.S. citizens, legal resident aliens, and those who have a work 
eligible visa. You may need to provide your social security number to receive payment. 
COSTS: If you participate in this study, the study will pay for those services, supplies, 
procedures, and care associated with the study that are not a part of your routine medical care.  
However, there may be additional costs to you.  These include basic expenses like transportation 
and the personal time it will take to come to the study visits.  You and/or your health insurance 
must pay for services, supplies, procedures, and care that are required during this study for 
routine medical care.  You will also be responsible for any co-payments and/or deductibles as 
required by your insurance.  Participation in this study is not a substitute for health insurance. 
SPONSOR: GE Healthcare is providing financial support and/or material for this study. 
 
Consultative or Financial Relationships: Dr. Andrei H. Iagaru is an unpaid consultant for GE 
Healthcare, the company sponsoring this study. 
 
CONTACT INFORMATION  
 
Questions, Concerns, or Complaints: If you have any questions, concerns or complaints 
about this research study, its procedures, risks and benefits, or alternative courses of 
treatment, you should ask the Protocol Director, Dr. Andrei Iagaru. You may contact him 
now or later at 
.  
 
Injury Notification: If you feel you have been hurt by being a part of this study, please 
contact the Protocol Director, Dr. Andrei Iagaru at 
. 
 
Independent Contact: If you are not satisfied with how this study is being conducted, or if 
you have any concerns, complaints, or general questions about the research or your rights as 
a participant, please contact the Stanford Institutional Review Board (IRB) to speak to 
someone independent of the research team at 
 
. 
 
Appointment Contact: If you need to change your appointment, please contact 
 
. 
 
Alternate Contact:  If you cannot reach the Protocol Director, please contact 
 
. 


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Andrei Iagaru, M.D. 
Protocol Title:    
68Ga- PSMA PET/MRI for detection of regional nodal and distant metastases in patients with 
intermediate and high-risk prostate cancer 
 
 
 
      
 
 
 
                          Page 12 of 14 
 
Participant ID: 
IRB Use Only 
Approval Date:   December 1, 2020 
Expiration Date:  December 1, 2021 
 
COMPENSATION 
All forms of medical diagnosis and treatment – whether routine or experimental – involve some 
risk of injury.  In spite of all precautions, you might develop medical complications from 
participating in this study.  If such complications arise, the Protocol Director and the research 
study staff will assist you in obtaining appropriate medical treatment.  In the event that you have 
an injury or illness that is directly caused by your participation in this study, reimbursement for 
all related costs of care first will be sought from your insurer, managed care plan, or other 
benefits program.  You will be responsible for any associated co-payments or deductibles as 
required by your insurance. 
 
If costs of care related to such an injury are not covered by your insurer, managed care plan or 
other benefits program, you may be responsible for these costs.  If you are unable to pay for such 
costs, the Protocol Director will assist you in applying for supplemental benefits and explain how 
to apply for patient financial assistance from the hospital. 
 
You do not waive any liability rights for personal injury by signing this form. 
 
EXPERIMENTAL SUBJECT’S BILL OF RIGHTS 
As a human subject you have the following rights. These rights include but are not limited to the 
subject's right to: 
 
be informed of the nature and purpose of the experiment;  
 
be given an explanation of the procedures to be followed in the medical experiment, and 
any drug or device to be utilized;  
 
be given a description of any attendant discomforts and risks reasonably to be expected;  
 
be given an explanation of any benefits to the subject reasonably to be expected, if 
applicable;  
 
be given a disclosure of any appropriate alternatives, drugs or devices that might be 
advantageous to the subject, their relative risks and benefits; 
 
be informed of the avenues of medical treatment, if any available to the subject after the 
experiment if complications should arise;  
 
be given an opportunity to ask questions concerning the experiment or the procedures 
involved;  
 
be instructed that consent to participate in the medical experiment may be withdrawn at 
any time and the subject may discontinue participation without prejudice;  
 
be given a copy of the signed and dated consent form; and  


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Andrei Iagaru, M.D. 
Protocol Title:    
68Ga- PSMA PET/MRI for detection of regional nodal and distant metastases in patients with 
intermediate and high-risk prostate cancer 
 
 
 
      
 
 
 
                          Page 13 of 14 
 
Participant ID: 
IRB Use Only 
Approval Date:   December 1, 2020 
Expiration Date:  December 1, 2021 
 
be given the opportunity to decide to consent or not to consent to a medical experiment 
without the intervention of any element of force, fraud, deceit, duress, coercion or undue 
influence on the subject's decision. 
Signing your name means you agree to be in this study and that you will receive a copy of this 
signed and dated consent form. 
 
_____________________________________ 
                
____________ 
Signature of Adult Participant 
 
 
 
   
Date 
 
 
_____________________________________             
 
Print Name of Adult Participant                                         
 
 
 
_____________________________________ 
                
____________         
Signature of Legally Authorized Representative (LAR) 
 
Date  
(e.g., parent, guardian or conservator)    
 
_____________________________________             
 
Print Name of LAR                                         
                             
  
_____________________________________ 
LAR’s Authority to Act for Participant  
 
 
(e.g., parent, guardian or conservator) 
 
 
 
_____________________________________ 
                
____________  
(If available) Signature of Other Parent or Guardian   
            Date       
                       
_____________________________________             
 
Print Name of Other Parent or Guardian                                         
 
_____________________________________ 
Authority to Act for Participant  
 
 
 
 
 
 
 
 


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Andrei Iagaru, M.D. 
Protocol Title:    
68Ga- PSMA PET/MRI for detection of regional nodal and distant metastases in patients with 
intermediate and high-risk prostate cancer 
 
 
 
      
 
 
 
                          Page 14 of 14 
 
Participant ID: 
IRB Use Only 
Approval Date:   December 1, 2020 
Expiration Date:  December 1, 2021 
 
 
_____________________________________ 
                
____________  
Signature of Person Obtaining Consent 
 
 
   
Date 
 
 
_____________________________________             
 
Print Name of Person Obtaining Consent 
 
 
 
The following witness line is to be signed only if the consent is provided as a summary form and 
accompanied by a short form foreign language consent. 
 
 
 
_____________________________________                       
____________ 
Signature of Witness                                                                
Date 
 
__________________________________              
Print Name of Witness 
(e.g., staff, translator/interpreter or family member) 
 
 Translated short form must be signed and dated by both the participant (or their LAR) AND the witness. 
 The English consent form (referred to as the "Summary Form" in the regulations): 
 Must be signed by the witness AND the Person Obtaining Consent (POC). 
 The non-English speaking participant/LAR does not sign the English consent. 
 The non-English speaking participant/LAR should not sign the HIPAA participant line 
 If the participant or the LAR is non-English speaking, the Person Obtaining Consent (POC) must ensure that 1) 
the LAR's Description of Authority is completed and 2) that any questions or options presented by the consent 
form are documented and initialed by the POC on the Summary Form, per the participant's wishes, as they are 
understood during the consent process.