Clinical trial NCT03302156
Conditions: Gynecologic Cancer
Keywords: Uterine cancer Ovarian cancer Hysterectomy Salpingo-oophorectomy
Sponsor: University of Wisconsin, Madison
Start date: 2017-11-15; Completion date: 2020-01-20
Enrollment: 15 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The goal of this research is to determine the accuracy of PSMA positron emission tomography (PET) and multi-parametric magnetic resonance (MR) imaging to detect the presence of gynecological cancer cells in the body.

Detailed description:
The investigators will evaluate a novel second-generation low-molecular-weight prostate specific membrane antigen (PSMA)-based positron emission tomography (PET) agent, 18F-DCFPyL, to determine the presence or absence of cancer, the accurate distribution of cancer and the normal biodistribution of PSMA in the abdomen and pelvis on PET imaging.

PSMA, also known as folate hydrolase 1 and glutamate carboxypeptidase II, is an enzyme associated with prostate cancer but has been also found to be expressed in the tumor neovasculature of many different types of non-prostate cancer tumors. PSMA-based 18F-DCFPyL PET demonstrates very high tumor-to-background ratio when studied in other tumors, including prostate tumors.

MR imaging is a highly sensitive and specific imaging modality that can be used for gynecologic cancers. MR images can be obtained in conjunction with PSMA PET, adding additional anatomic and multi-parametric MRI information without the need for a second imaging appointment.

Arms: arm 1: The control group will consists of women with no imaging evidence of gynecological cancer, who are undergoing hysterectomy and salpingo-oophorectomy. Women will receive PSMA-based 18F-DCFPyL tracer and PET/MR imaging. n=6 arm 2: The patient group will consist of women with suspected gynecological cancers who are undergoing hysterectomy and salpingo-oophorectomy. Women will receive standard of care PSMA-based 18F-DCFPyL tracer and PET/MR imaging. n=40 arm 3: Women with or without suspected gynecological cancer. Women will receive PSMA-based 18F-DCFPyL tracer and PET/CT imaging, PET/MR imaging as needed. n=6
Interventions: intervention 1: PSMA-based 18F-DCFPyL PET tracer
Intervention descriptions: intervention 1: PSMA-based 18F-DCFPyL PET tracer that will be used to determine the presence or absence of cancer

Protocol documents:
Prot_SAP_000.pdf: 
1 
 
PSMA Positron Emission Tomography (PET) and 
Magnetic Resonance (MR) Imaging in Gynecological 
Cancers 
 
UW IRB Tracking # 2017-0456 
 
NCT03302156 
 
 
Principal Investigator: 
 
Steve Cho, MD 
University of Wisconsin, School of Medicine & Public Health 
Department of Radiology 
 
Co-Principal Investigators: 
 
Elizabeth Sadowski, MD 
University of Wisconsin, School of Medicine & Public Health 
Departments of Radiology, Obstetrics and Gynecology 
 
Lisa Barroilhet, MD 
University of Wisconsin, School of Medicine & Public Health 
Departments of Obstetrics and Gynecology 
 
 
 
 
 
 
Funding Sponsor: UWCCC Imaging and Radiation Science Pilot Award 
 
 
 
June 8, 2020 
 
 
 
 


2 
 
Protocol Revision History 
Version Date 
Summary of Revisions Made 
15 FEB 2017 
Original Version 
07 APR 2017 
Addition of a follow-up phone call 1-3 days post PET/MR imaging exam. 
10 APR 2017 
Revise biodistribution and radiodosimetry procedures for aim 1 
02 MAY 2017 
Updated statistics 
17 OCT 2017 
PET/CT replacing PET/MR for dosimetry studies; correcting imaging time; 
revising eligibility; make glucagon optional. 
25 JAN 2018 
Revise exclusion criteria to allow women with a history of cancer to participate. 
10 July 2018 
Revise inclusion criteria to allow women with a history of gynecological cancer, 
hysterectomy and/or salpingo-oophorectomy to participate; addition of blood and 
urine samples for dosimetry subjects 
05 NOV 2019 
Clarifications to dosimetry cohort; edits made for consistency in 18F-DCFPyL 
dosing.  The dose should be “less than 9 mCi” 
08 JUN 2020 
Revised blood collection for dosimetry subjects and removed the urine collection 
requirement.  Revisions to the consenting process during the COVID-19 
pandemic. 
 
 


3 
 
Table of Contents 
 
LIST OF ABBREVIATIONS 
STATEMENT OF COMPLIANCE 
PROTOCOL SUMMARY 
SCEMATIC OF STUDY DESIGN 
1.0 
Project Summary 
2.0 
Introduction 
3.0 
Study Aims/Study Objectives 
4.0 
Research Design and Methods 
5.0 
Study Procedures 
6.0 
Risks and Benefits 
7.0 
Adverse Events and Safety Issues 
8.0 
Privacy and Confidentiality Protections 
9.0 
Data and Safety Monitoring 
10.0 Statistical Considerations 
11.0 Drug Formulation and Procurement 
12.0 References 
 
 


4 
 
LIST OF ABBREVIATIONS 
AE 
Adverse event 
CAEPR 
Comprehensive Adverse Events and Potential Risks 
CT 
Computed tomography 
CTCAE 
Common Toxicity Criteria for Adverse Events 
DSMB/DSMC 
Data Safety Monitoring Board/Committee 
FDA 
Food and Drug Administration 
GE 
General Electric 
GFR 
Glomerular filtration rate 
HIPAA 
Health Insurance Portability and Accountability Act 
IEC 
International Electrotechnical Commission 
IRB 
Institutional Review Board 
IV 
Intravenous 
IND 
Investigational New Drug 
kg 
kilogram 
MBq 
megabecquerel  
mCi 
millicurie 
mGy 
milligray 
mL 
milliliter 
mmol 
millimole 
MR 
Magnetic Resonance 
OB/Gyn 
Obstetrics and Gynecology 
PACS 
Picture Archiving and Communication System 
PET 
Positron Emission Tomography 
PI 
Principal Investigator 
PSMA 
Prostate-specific member antigen 
REM 
Roentgen Equivalent Mammal 
RF 
Radio frequency 
RPF 
Radiopharmaceutical Production Facility 
SAE 
Serious Adverse Event 
UP 
Unanticipated Problem 
UW 
University of Wisconsin 
UWHC 
University of Wisconsin Hospital and Clinics 
 
 
 
 
 


5 
 
STATEMENT OF COMPLIANCE 
 
The signature below constitutes the approval of this protocol and the attachments, and provides 
the necessary assurances that this trial will be conducted according to all stipulations of the 
protocol, including all statements regarding confidentiality, and according to local legal and 
regulatory requirements and applicable US federal regulations and ICH guidelines. 
 
I agree to ensure that all staff members involved in this study are informed about their 
obligations in meeting the above commitments. 
 
 
Principal Investigator:  Steve Y. Cho, MD 
 
 
Signed: 
 
 
 
 
 
 
Date: 
 
 
__________________________________   
 
__________________ 
 
 
Steve Y. Cho, M.D. 
Department of Radiology, Nuclear Medicine Section 
University of Wisconsin School of Medicine and Public Health 
University of Wisconsin Carbone Comprehensive Cancer Center 
 
 


6 
 
PROTOCOL SUMMARY 
 
Title 
PSMA PET and Magnetic Resonance (MR) Imaging in Gynecological Cancers 
IND Sponsor-
Investigator 
Steve Y. Cho, MD 
Co-Investigators 
Elizabeth Sadowski, MD; Lisa Barroilhet, MD 
Participating Site 
University of Wisconsin-Madison  
Patient Population 
1. Adult women with known or suspected gynecological cancers who have had or 
are scheduled to undergo a hysterectomy and/or salpingo-oophorectomy. N=40 
2. Normal controls: Women with no imaging evidence of gynecological cancer, 
who are undergoing hysterectomy and/or salpingo-oophorectomy. N=12 (includes 
up to 6 Dosimetry subjects) 
a. Dosimetry : Women with or without suspected gynecological cancer.  
Accrual Objective 
52 women  
Study Design 
Phase 2, single-center, open-label study  
Study Duration 
The estimated accrual period is over 3 years. 
Primary Objective 
The purpose of this research is to evaluate whether a novel imaging approach 
using PSMA-based 18F-DCFPyL PET and MR imaging can: 
1. Document the normal distribution of PSMA in the abdomen and pelvis on PET 
imaging. 
2. Document the normal appearance of the fallopian tubes and ovaries on high 
resolution MR imaging  
3. Accurately determine the presence or absence of cancer  
4. Accurately identify the distribution of cancer 
Specific Aims 
1. To establish the biodistribution and radiodosimetry of PSMA-based 18F-DCFPyL 
on PET imaging in normal female controls and in females with known or 
suspected cancer. 
2. To determine the ability of PSMA-based 18F-DCFPyL PET and MR imaging to 
detect cancer in women with known or suspected  gynecologic malignancy and 
differentiating cancerous tissue from non-cancerous tissue.  The performance 
of PSMA-based 18F-DCFPyL PET imaging in the detection and localization of 
cancerous and non-cancerous tissue will be compared to the final surgical 
pathology reports and to the histological and immunostaining for PSMA 
positive cancerous tissue on pathology. 
3. To determine the most accurate approach in assessing disease burden and 
location, assessment of tumor burden on both the PSMA-based 18F-DCFPyL PET 
and MR imaging together, and then each modality separately will be 
performed and sensitivity, specificity, and accuracy values will be calculated. 
Inclusion Criteria 
• 
Women with no imaging evidence of cancer  
• 
Women with suspected or documented gynecological cancer  and previously 
underwent or scheduled to undergo a hysterectomy and/or salpingo-
oophorectomy 
• 
No contraindications for MR or PET imaging. 
• 
Greater than or equal to 18 years 
Exclusion Criteria 
• 
Women that are pregnant or breast feeding. 
• 
Age <18  


7 
 
• 
Severe kidney dysfunction (GFR <30 mL/min/1.73m2) 
Treatment 
Description 
18F-DCFPyL whole body PET/CT or PET/MR scan 
Study Procedures 
• 
18F-DCFPyL whole body PET/CT imaging for dosimetry studies; PET/MR scan 
to achieve other aims 
• 
Review of relevant imaging and medical record information 
Statistical 
Considerations 
There are no formal hypothesis tests planned.   
Our primary goals are to: 
1. Record the normal biodistribution and radiodosimetry of PSMA in the body 
2. Record the frequency the normal fallopian tubes and ovarian are seen on high 
resolution MR imaging. 
3. Record the distribution of PSMA in cancer tissue 
4. Estimate the frequency with which PSMA PET and MR imaging and final IHC 
staining disagree in their classifications of presence of disease.  We will classify each 
data point as either an agreement or disagreement between imaging findings and 
IHC staining.  The proportion of disagreements across all time points will be 
estimated with an intercept-only GEE regression model that accounts for 
correlation among measures from the same patient.  This proportion will be 
reported with a 95% confidence interval.  The lower bound of this confidence 
interval will be used to help us decide whether this approach is worthy of future 
study.  Based on this pilot study we plan to pursue further evaluation in larger more 
appropriately powered studies if the lower bound of the confidence interval 
excludes 20%, which is chosen as a guideline to determine whether the method 
shows promise. 
 
 


8 
 
SCHEMATIC OF STUDY DESIGN 
 
Subject Populations 
 
 
 
 
 
 
  
 
 
 
 
 
 
   
 
 
 
 
STANDARD OF CARE SURGERY 
 
 
 
 
 
 
 
 
IMAGING PROTOCOL 
(Dosimetry) 
 

Imaging = WB PET/CT; opt WB PET/MR 
Up to 6 subjects (with or without 
cancer) 
Administration of less than 9 mCi of 
18F-DCFPyL in the PET/CT scanner 
•
Up to 120 minutes of whole body 
PET scanning 
•
If time permits a whole body 
PET/MRI will also be conducted 
 
 
IMAGING PROTOCOL 
(Main Study) 
 

Imaging = WB PET/MR only 

52 less the number of subjects that 
participated in the “Dosimetry” 
protocol. 
•
Administration of less than 9 
mCi of 18F-DCFPyL 
•
60 minute uptake period, 
outside of scanner 
•
Administration of Glucagon prior 
to PET/MR imaging (as needed) 
•
Whole body PET/MR scanning 
for up to 90 minutes 
 
Healthy controls (n=12) 
 
Patients with known gynecologic 
cancer (n=40) 
IMMUNOHISTOCHEMISTRY 
•
Structures that were positive on18F-DCFPyL based PSMA PET imaging will be stained to confirm the presence of 
both PSMA on immunohistochemistry and active cancer on histology evaluation. 
•
The uterus and ovarian will be stained with PSMA and correlated with imaging,  


9 
 
1.0 
PROJECT SUMMARY:  
The purpose of our proposal is to use PSMA PET and multi-parametric MR imaging, to detect the 
presence of gynecological cancer cells in the body. Imaging evaluation would include the 
appearance of normal ovaries/fallopian tubes, and cancerous tissue on different MR sequences 
and the distribution of PSMA in normal and pathological tissues on PET images. To determine 
the accuracy of the PSMA PET imaging localization in malignant tissues, PSMA staining of 
surgical pathology specimens will be used as the reference standard. 
 
2.0 
INTRODUCTION 
Background: 
The detection and distribution of cancer prior to definitive treatment is the standard of care 
currently [1]. Imaging plays a crucial role in this process of identifying possible areas of tumor 
prior to initiation of treatment [2]. Currently, imaging techniques used in clinical practice to 
visualize cancer mainly involve basic cross sectional anatomical imaging with or without 
intravenous contrast administration. These imaging techniques are limited by only providing 
“anatomical” information, and the diagnosis of cancer and normal tissue is partly determined by 
the location of the tissue. Imaging contrast agents can help visualize abnormalities, but currently 
cannot differentiate between malignant, inflammatory or fibrotic (scar) tissues.  There have been 
major research advancements in functional imaging, which allow the physician to determine better 
what type of tissue is present in an anatomical location. Advanced PET and MR imaging 
techniques can evaluate the chemical composition and metabolic activity of different tissues [3, 
4]. MR imaging can depict the composition of tissue (water, fat, blood and cellular) by imaging the 
molecules in the human body. PET imaging can depict whether or not tissue is metabolically 
active by imaging the injectable metabolic tracer which is taken up by different area or tissue types 
in the body. Knowing both the composition of the tissue and the metabolic fingerprint can help 
differentiate more accurately between non-cancerous and cancerous tissue types [5]. This in turns 
allows for more accurate cancer screening and pre-treatment staging, both which have been 
shown to improve outcomes in gynecologic cancer patients [1, 6]. 18F-FDG PET imaging is widely 
used for cancer detection and staging, but can be limited due to nonspecific uptake at sites of 
inflammation.  A more specific PET imaging agent for more specific tumor detection, particularly 
in gynecologic malignancy, would help meet an unmet clinical need.     
PSMA, also known as folate hydrolase 1 andglutamate carboxypeptidasse II, is an enzyme 
associated with prostate cancer but has been also found to be expressed in the tumor 
neovasculature of many different types of non-prostate cancer tumors [7, 8]. The PSMA molecule 
can be bound to a PET radionuclide as an imaging agent, specifically, 18F-DCFPyL, and this agent 
can be detected non-invasively using PET imaging.  PSMA-based 
18F-DCFPyL PET 
demonstrates very high tumor-to-background ratio when studied in other tumors, including 
prostate tumors [9]. In prostate cancer, the agent has been shown to improve detection of prostate 
tumors and the amount of tumor present throughout the body (tumor burden). Similar high tumor-
to-background uptake of PSMA-based PET imaging has been demonstrated targeting the tumor 


10 
 
neovasculature of non-prostate solid tumors (example: renal cell carcinoma and lung) with 
potential improved tumor specificity [10, 11]. There is growing evidence in the literature which 
demonstrates that correctly identifying the tumor burden allows the treating physician to tailor the 
treatment more specifically to the individual patient to assure all the cancer cells are treated [12]. 
Recently, an immunohistologic pathology study demonstrated PSMA is highly and specifically 
expressed in the tumor vasculature of ovarian and uterine tumor specimens [9]. This makes 
exploring PSMA as a potential functional imaging agent for ovarian cancer very intriguing. 
MR imaging is a highly sensitive and specific imaging modality that can be used for gynecologic 
cancers. MR images can be obtained in conjunction with PSMA PET, adding additional anatomic 
and multi-parametric MRI information without the need for a second imaging appointment. 
Emerging data demonstrates that the inclusion of functional MR sequences, specifically diffusion 
weighted sequences, increases the sensitive and specificity of MR imaging in the detection of 
tumors, including metastatic cancer deposits [3, 5]. 
The overarching goals of this pilot study are to determine if imaging can depict PSMA 18F-DCFPyL 
uptake in gynecological cancers seen on MR imaging, and to correlate both the PSMA PET and 
MR imaging with histological and immunologic staining of resected tumor specimens in women 
undergoing the standard of care surgical treatment of their gynecological cancers.  If it is possible 
to see PSMA on acquired images, PSMA 18F-DCFPyL could potentially be used for both screening 
and pre-treatment assessment of women with gynecologic cancers with improved sensitivity and 
specificity. 
3.0 
STUDY AIMS/STUDY OBJECTIVES  
The primary outcome of this research is to evaluate whether a novel imaging approach using 
PSMA-based 18F-DCFPyL PET and MR imaging can accurately determine the presence or 
absence of cancer, the accurate distribution of cancer and the normal biodistribution of PSMA in 
the abdomen and pelvis on PET imaging.  The reference standard for the PSMA localization in 
cancerous tissue will be histologic and immunologic correlation on the pathologic specimens 
obtained at the time of standard of care surgical resection for treatment of the gynecological 
cancer.  Specific aims for this research include the following: 
1.  To establish the biodistribution and radiodosimetry of PSMA-based 18F-DCFPyL on PET 
imaging in normal female controls and in females with known or suspected cancer. 
2.  To determine the sensitivity, specificity, and accuracy values of PSMA-based 18F-DCFPyL 
PET and MR imaging in the detection of cancer in women with known or suspected 
gynecologic malignancy and differentiating cancerous tissue from non-cancerous tissue.  
The performance of PSMA-based 18F-DCFPyL PET imaging in the detection and 
localization of cancerous and non-cancerous tissue will be compared to the final surgical 
pathology reports and to the histological and immunostaining for PSMA positive cancerous 
tissue on pathology. 
3. To determine the most accurate approach in assessing disease burden and location, 
assessment of tumor burden on both the PSMA-based 18F-DCFPyL PET and MR imaging 


11 
 
together, and then each modality separately will be performed and sensitivity, specificity, 
and accuracy values will be calculated. 
 
4.0 
RESEARCH DESIGN AND METHODS:  
Subject population 
Fifty-two subjects will be enrolled in this research, 12 healthy controls and 40 patients with known 
or suspected gynecologic cancer. Up to 6 subjects will be used for the dosimetry portion.     
Eligibility requirements include the following: 
Inclusion Criteria for healthy female controls  N=12 (includes up to 6 Dosimetry subjects) 
1. Women with no suspected gynecological cancer 
2. No contraindications for MR or PET imaging 
3. Greater than or equal to 18 years of age 
4. Scheduled to undergo a hysterectomy and/or salpingo-oophorectomy  
 
Inclusion Criteria for female controls (Dosimetry)  
1. Women with or without suspected gynecological cancer 
2. No contraindications for MR or PET imaging 
3. Greater than or equal to 18 years of age 
 
Inclusion Criteria for gynecologic cancer patients N=40 
1. Women with known or suspected gynecological cancer  
2. No contraindications for MR or PET imaging. 
3. Greater than or equal to 18 years 
4. Have had or are scheduled to undergo a hysterectomy and/or salpingo-oophorectomy 
 
Exclusion Criteria 
1. Women that are pregnant or breast-feeding. 
2. Age <18  
3. Inability to provide informed consent on their own behalf 
4. Severe kidney dysfunction (GFR <30 mL/min/1.73m2) 
 
Subject identification and recruitment  
Healthy controls will be recruited from UWHC OB/Gyn and Women’s Health and PATHS clinics 
through referrals and from posted flyers. Healthy controls may also be recruited from the 
Department of Radiology Volunteer Database (2017-0004).  Potential subjects will either be 
introduced to the research by someone involved in their care or they will be required to contact 


12 
 
the study team by phone or email.  Those interested in participating will be scheduled for an initial 
visit to learn more about participation and to complete the informed consent process.   
Gynecologic Oncology staff will identify cancer patients who meet the eligibility criteria and will 
introduce them to this research opportunity.  Those interested will be referred to a study team 
member who will review the purpose of the research as well as details about participation.   
Informed Consent and Subject Information 
The consent process will occur either on a day prior to or on the day of but prior to the 
administration of research procedures.  During the COVID-19 pandemic, consent procedures will 
be conducted by phone to minimize face-to-face contact subjects have with the research team.  
An encrypted copy of the consent form will be mailed or emailed to subjects prior to the scheduled 
consent phone call.  A study team member will call potential subjects at the scheduled time to 
review the information in the consent form including study procedures, risks associated with 
participation, alternatives to participation and whom to contact for additional information.  Any 
questions will be addressed during the course of the phone call and subjects will be encouraged 
to contact the study team with any questions or concerns they might have at any time.  Upon 
completion of the consent process, subjects will be asked to return a copy of the signed consent 
form by either scanning the entire document and email back to the study team member or taking 
a photo of the signature page and emailing a copy to the study team member.   
Once institutional requirements are met, remote consenting will continue by obtaining electronic 
signature using the DocuSign software platform. 
Prior to the start of any research procedures and all subjects will be reminded that participation is 
optional and they can change their mind at any time. 
 
5.0 
STUDY PROCEDURES 
Subjects will be asked to complete a single research visit that will include the administration of a 
PSMA PET/CT and/or PET/MR exam.  Subjects participating in the PET/MR imaging studies will 
be screened for contraindications to MRI and MR contrast agents using the standard UWHC MR 
Safety screening form. A urine pregnancy test will only be done for women with childbearing 
capacity that are unable to verify their non-pregnancy status by self-report.  
Aim 1. Biodistribution and radiodosimetry of PSMA-based 18F-DCFPyL in normal female controls 
or cancer patients (Up to 6 subjects for non-dosimetryand 6 subjects for radiodosimetry 
(dosimetry) 
The research visit is estimated to take 2-3 hours, which includes approximately 60-120 minutes 
of scanning time. Subjects will be asked to fast for 4 to 6 hours prior to the research visit and to 
stay well hydrated. 
The remainder of the time will be preparatory for the scanning. An IV will be placed to allow 
injection of the PET tracerduring the exams.   


13 
 
Dosimetry Subjects: A less than 9 mCi dose of 18F-DCFPyL radiotracer will be administered by 
slow IV push after subject has been positioned in the PET/CT scanner. The subject’s imaging 
session will include multi-pass PET scans to allow for normal organ and tumor biodistribution for 
a total of 5 PET scans from the vertex of skull through mid-thigh.  Initial low-dose CT will be 
followed by 4 PET scans (PET1 through PET4) lasting approximately 60 to 75 minutes (depending 
on the height of the patient). The subjects will be allowed to leave the table to void between the 
fourth and fifth (PET5) PET scans. The fifth PET/CT scan (PET5) is obtained with another low-
dose CT scan to allow for CT attenuation correction followed by the PET scan starting at 
approximately 90 minutes after radiotracer administration to last up to approximately 30 minutes 
(again, depending on the height of the patient).  If the PET/CT takes less than 120 minutes, the 
subject may undergo a PET/MR, as time allows. 
Dosimetry Subjects Only - Blood Collection:  
• 
Blood (5mL Purple top at each time point) will be collected at 3 time points, after the 
completion of the 2nd, 4th and 5th PET passes on the PET dosimetry PET/CT protocol.  
Blood will be collected for the first 3 subjects and as needed for the remaining 3 subjects. 
• 
Blood and will be counted on a gamma counter after dilution to determine radioactivity on 
the same day as the scan.  After radioactive decay overnight, blood will be disposed of as 
per routine biohazard. 
Non-dosimetry subjects: An IV will be placed to allow injection of the PET tracer, MR gadolinium 
agent, and glucagon (if needed) during the exams.  A less than 9 mCi dose of 18F-DCFPyL 
radiotracer will be administered by slow IV push outside the scanner, after which, the subject will 
be required to sit quietly for 60 minutes to allow for adequate biodistribution of the tracer. The 
subjects will then be placed in the PET/MR scanner and will remain in the scanner for up to 90 
minutes.  After which, the whole body (defined in this protocol as base-of-skull to mid-thigh) PET 
and MR images will be obtained to include images post-intravenous gadolinium contrast. 
Glucagon (0.5mg-1mg, IV) may be administered by IV prior to the MR imaging if excessive bowel 
movement is seen on initial images. Glucagon is known to diminish bowel motion and improve 
MR image quality.  
Aims 2 & 3. Sensitivity, specificity, and accuracy values of PSMA-based 18F-DCFPyL PET and 
MR imaging and assessment of tumor burden (40 subjects with known or suspected 
gynecological cancer). 
This research visit is estimated to take 2-3 hours. For subjects with gynecologic cancer, the 
subjects will be in the scanner for up to 90 minutes. The remainder of the time will be preparatory 
for the scanning.  An IV will be placed to allow injection of the PET tracer, MR gadolinium agent, 
and glucagon (if needed) during the exams.  Subjects will be asked to fast for 4 to 6 hours prior 
to the research visit and to stay well hydrated. There will be a 1-hour uptake period after IV 
administration of less than 9 mCi of 18F-DCFPyL radiotracer by slow IV push. After which, the 
whole body (defined in this protocol as base-of-skull to mid-thigh) PET and MR images will be 
obtained to include images post-intravenous gadolinium contrast. Glucagon (0.5mg-1mg, IV) may 


14 
 
be administered by IV prior to the MR imaging if excessive bowel movement is seen on initial 
images. Glucagon is known to diminish bowel motion and improve MR image quality.  
A member of the study team will follow-up with all subjects approximately 1 to 3 days, by phone, 
after their PET/MRI or PET/CT exam to inquire about delayed side effects.  If the subject is 
experiencing any late occurring side effects, they will be asked to return to the research clinic for 
a follow-up exam.  
All PET and MR hardware are FDA approved as are the PET and MR sequences to be used.  
Histopathological, Immunologic Staining and Image Correlation  
We will correlate the final surgical pathology report with the images to determine if all sites of 
disease were seen on PSMA PET and MR imaging. In addition to this, we will identify very specific 
sites (eg. Left obturator node; Right ovarian mass; etc) for PSMA immunologic staining pre-
operatively by review of the imaging between the radiologist and the gynecologic oncology 
surgeon and the surgeon will make every attempt to send these PSMA specimens labeled and 
separate from the other specimens obtain during surgery.  
The surgical pathology specimens will be processes per routine clinical protocol. The same tissue 
blocks used for routine pathological evaluation will be used for the immunolabeling of the PSMA 
in the TRIP lab. After the clinical processing is complete, the pathologist with choose the 
appropriate tissue block(s) for immunolabeling, which consumes only a minute amount of tissue. 
This process will in no way compromise patient care. 
Review of Medical Records 
Medical records will be reviewed to obtain medical history including physical exams, medications, 
laboratory tests, imaging results and any other information related to the diagnosing, treatment, 
or outcomes of subjects diagnosis. 
Remuneration 
Subjects will receive $100 as compensation for their participation in this study. 
Study Withdrawal 
Reasons for withdrawal or termination  
Enrolled patients will be removed from the study in the following circumstances: 
• 
The patient does not complete the imaging examinations per study protocol 
• 
The subject withdraws consent 
• 
Exclusion criteria are discovered after registration but prior to the research 
examinations 
• 
The patient has a contrast reaction to the gadolinium based contrast agent utilized 
for the MRI 
• 
The PI or co-investigators determine it is within the best interest of the subject to 
remove them from the research. 


15 
 
 
6.0 
RISKS AND BENEFITS 
PET: 
Detailed organ dosimetry derived from four representative patients is included in the table below.  
Of note, the effective dose from 18F-DCFPyL was 0.0165 mSv/MBq or 6.1 mGy (0.61 rem) for an 
injected dose of 370 MBq (10 mCi), or 5.49 mGy or 5.49 mSv (0.549 rem) for 333 MBq (9 mCi) 
which is the highest dose administered for this study.   
Dosimetry:   
Highest radiation dose was estimated for the kidneys (0.0945 mGy/MBq) followed by urinary 
bladder wall (0.0864 mGy/MBq), submandibular glands (0.0387 mGy/MBq) and liver (0.0380 
mGy/MBq). The mean absorbed dose to the bone marrow was 0.01 mGy/MBq.  In comparison to 
the published data on our first generation agent, 18F-DCFBC, 18F-DCFPyL shows significantly 
lower (under 50 %) doses in most radiosensitive organs such as the thymus, ovaries, red marrow 
and osteogenic cells. Less radiation dose was also measured in lower large intestinal wall, small 
intestine, stomach wall, lungs, muscle and skin. Radiation dose from the two radiotracers was 
similar (within +/-50 %) in the gallbladder wall, upper large intestinal wall, spleen, testicles, thyroid, 
and pancreas.  Radiation dose from 18F-DCFPyL was higher in the adrenals, kidneys, liver, 
pancreas, spleen, and bladder wall. 
 
Organ 
Absorbed 
Dose 
(mGy/MBq) 
 
Organ 
Absorbed 
Dose 
(mGy/MBq) 
Adrenals 
3.11E-02 
 
Ovaries 
8.89E-03 
Brain 
2.19E-03 
 
Pancreas 
2.44E-02 
Breasts 
4.57E-03 
 
Parotid Glands 
2.68E-02 
Gallbladder Wall 
1.44E-02 
 
Red Marrow 
1.04E-02 
Heart Wall 
1.29E-02 
 
Skin 
4.05E-03 
Kidneys 
9.45E-02 
 
Small Intestine 
9.13E-03 
Lacrimal Glands  
3.50E-02 
 
Spleen 
1.85E-02 
Lens 
1.25E-03 
 
Stomach Wall 
1.16E-02 
Liver 
3.80E-02 
 
Submandibular Glands 
3.87E-02 
LLI Wall 
1.05E-02 
 
Testes 
1.01E-02 
Lungs 
1.08E-02 
 
Thymus 
5.56E-03 
Muscle 
6.32E-03 
 
Thyroid 
8.56E-03 
Osteogenic Cells 
9.58E-03 
 
ULI Wall 
1.67E-02 
Urinary Bladder Wall 
 
8.64E-02 
 
Uterus 
1.15E-02 
 
CT:   
Low-dose CT imaging is used to provide attenuation correction for the PET scan and PET signal 
localization.  The addition radiation dose associated with this imaging is approximately 1.0 rem or 
10 mSv.  For the dosimetry PET/CT scans, there will be two low-dose CT scans obtained for a 
total of approximately 2.0 rem or 20 mSy. 


16 
 
MR:   
Because the MR scanner is comprised of a very strong magnet, the primary risk associated with 
MRI imaging is the risk of having ferrous metal in the body such as pins, rods, screws, 
pacemakers, etc. 
 
Risks will be minimized by making subjects feel as comfortable as possible in the PET/MR 
scanner.  They will be repositioned and provided with as much padding as needed.  Subjects will 
be able to communicate with the imaging staff in the event they decide they cannot continue to 
lie still for the duration of the study, in which case the study procedure will be terminated. Potential 
subjects who are asked to participate in MR imaging will be screened for contraindications to MRI 
and gadolinium contrast. 
 
Gadolinium based contrast agents: Gadobenate dimeglumine be administered according to a 
weight-based algorithm (0.1 mmol/kg), not to exceed 20 mL.  The risks of administering a 
gadolinium-based agent are exceedingly low; common side effects may include headache, 
nausea, reaction at injection site, and vasodilatation (temporary widening of a blood vessel) that 
occurred in less than 3% of subjects. Other less-common side effects reported were bad taste in 
the mouth, skin rash, dizziness, or warm tingling or burning feeling on the skin.  
 
Acute allergic reactions are extremely uncommon, far less common than occur with iodine-based 
contrast agents used in CT scanning. To treat unexpected contrast reactions, we maintain a fully 
up-to-date contrast reaction/resuscitation kit adjacent to our scanners in the UWHC Department 
of Radiology. The contrast reaction kit is identical to those used throughout our department to 
treat allergic reactions to iodinated contrast or gadolinium based contrast agents, and is fully 
stocked with all necessary medications to treat contrast reactions. Further, there is always an 
experienced radiologist who is trained in treating contrast reactions available within the UWHC 
during working hours, for this purpose.  
 
There are no immediate benefits anticipated for the participants. This research has a long-term 
benefit of validating the feasibility of a PET/MR imaging technique with enhanced diagnostic, 
prognostic and treatment response monitoring capabilities. Ultimately, this trial may allow us to 
perform PET scans in a much shorter period of time and achieve better quantification.  
 
Glucagon:  Contraindications to glucagon include known hypersensitivity to the drug, known 
pheochromocytoma or insulinoma. Subjects that are diabetic will not be given this drug.  The 
nurse administering glucagon will screen subjects for a history of diabetes prior to its 
administration.  Glucagon is typically well tolerated and is rapidly metabolized with a half-life of 
approximately 8-18 minutes. 
 
Blood Collection: The blood sample will be collected via IV. Subjects may experience some 
discomfort, minor bruising, bleeding, or inflammation in the area where the blood is drawn. They 
may also experience nausea, lightheadedness, or fainting associated with this blood draw. There 
is also a very small chance (less than 1%) of infection at the needle puncture site. 
 


17 
 
 
7.0 
ADVERSE EVENTS AND SAFETY ISSUES 
Definition of adverse events and potential risks: The term “adverse event” is defined in the 
International Conference on Harmonization Guideline for Good Clinical Practice as follows: “Any 
untoward medical occurrence in a patient or clinical investigation subject administered a 
pharmaceutical product and which does not necessarily have a causal relationship with this 
treatment.  An adverse event (AE) can therefore be any unfavorable and unintended sign 
(including an abnormal laboratory finding), symptom, or disease temporally associated with the 
use of a medicinal (investigational) product whether or not related to the medicinal 
(investigational) product”.  
Medical conditions of a subject that exist prior to receiving the investigational imaging tracer will 
be recorded as medical history.  After administration of the investigational imaging tracer, all new 
medical conditions are considered adverse events.  Adverse events occurring in this trial will be 
recorded in data collection forms, regardless of whether or not they are thought to be associated 
with the investigational imaging tracer throughout the study period.  However, the Investigator 
also will assess the possible relationship between the adverse event and the investigational 
imaging tracer. 
For the purposes of this protocol, an adverse event (AE) is any untoward medical occurrence 
(e.g., sign, symptom, disease, syndrome, intercurrent illness, abnormal laboratory finding) that 
emerges or worsens relative to pre-imaging baseline. We anticipate minimal adverse effects or 
toxicity with the investigational imaging tracer 18F-DCFPyL in this study.  
Definition of Serious Adverse Events (SAE), SAE list: Any adverse drug experience, occurring 
at any dose that results in any of the following: 
• 
Death 
• 
Is life-threatening (an event in which the patient was at immediate risk of death; it 
does not refer to an event which hypothetically might have caused death if it were 
more severe) 
• 
Requires or prolongs inpatient hospitalization  
• 
Results in a persistent or significant disability/incapacity 
• 
Is a congenital anomaly/birth defect 
• 
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered serious when, based upon appropriate medical 
judgment, they may jeopardize the patient or subject and/or may require intervention 
to prevent one of the outcomes listed. 
 
All other AEs will be treated as “non serious” and are described in the final study report.  An SAE 
that is definitely, probably or possibly related to the investigational imaging tracer will be reported 
immediately (within 24 hours of its determination) by telephone or fax by the Principal Investigator. 
 


18 
 
AE Characteristics: Toxicity will be graded according to the NCI Common Toxicity Criteria 
(CTCAE), version 4.03 (Appendix A; which can also be accessed and downloaded via the 
website: http://ctep.cancer.gov/reporting/ctc.html. The Investigators will monitor the occurrence 
of adverse events during the course of each patient in the study. The Investigators need to assess 
whether there is a reasonable possibility that the study imaging agent caused or contributed to an 
AE using the following criteria as a guide: 
• 
Definite: The adverse event is clearly related to the investigational agent. 
 
• 
Probable: There is a clinically plausible time sequence between the onset of the AE 
and administration of imaging tracer.  The AE is unlikely to be caused by the 
concurrent/underlying illness, other drugs, or procedures.  
 
• 
Possible: There is a clinically plausible time sequence between the onset of the AE 
and administration of imaging tracer, but the AE could also be attributed to the 
concurrent/underlying disease, other drugs, or procedures.  “Possibly” should be used 
when the administration of the study imaging tracer is one of several biologically 
plausible causes of the AE. 
 
• 
Unlikely: The adverse event is doubtfully related to the investigational imaging tracer. 
 
• 
Not Related: Another cause of the AE is the most plausible and/or a clinically plausible 
temporal sequence is inconsistent with the onset of the AE and the investigational 
imaging tracer; and/or a causal relationship is considered biologically implausible. 
 
If any adverse event is considered to be definitely, possibly or probably related to the 
investigational imaging tracer, that event will be followed until resolution or until it is deemed 
chronic or irreversible by the Investigator.  If an event is unlikely or not related to the investigational 
imaging tracer, the event will not be reported. 
 
All AE will be documented and recorded in the medical record and will include: 
 
I. 
Specific reaction according to NCI Common Toxicity Criteria, version 4.0. 
 
II. 
Duration of the reaction 
 
III. 
Severity/grade according to NCI Common Toxicity Criteria, version 4.03. If the adverse 
event is not addressed by the Common Toxicity Criteria, the severity should be rated 
as mild (grade 1), moderate (grade 2), severe (grade 3), or life threatening (grade 4). 
 
IV. 
Relation of reaction to study agent 
 


19 
 
V. 
Management of reaction, including any interruption or dose modification of the study 
drugs. 
 
 
Event Severity: In addition to classifying an adverse event as serious or non-serious, the 
Investigator and/or designated personnel will grade the adverse event to  describe 
The 
Maximum intensity of the event.  Specific criteria for the intensity of adverse events are described 
in the Common Toxicity Criteria (CTC:  National Cancer Institute).  Investigators should follow 
these criteria for grading and reporting adverse events. 
An event may be severe, but may not be serious (e.g., severe headache).  The severity  of 
an 
adverse event will be assessed by study personnel using their best clinical judgment and includes 
but is not limited to taking into account the patient’s past history, the patient’s chart, interviews 
with the patient and caregivers, and direct observation.  The Investigator will also be asked to 
assess the possible relationship between the adverse event and the administration of the 
investigational imaging tracer. 
Adverse Event Reporting: Per 21CFR312.32(c), all adverse events deemed both serious and 
unexpected associated with the use of the drug must be reported to the FDA and to all 
participating investigators as soon as possible and in no event later than 15 days. 
The FDA will be notified of any unexpected fatal or life threatening experience associated with 
the drug as soon as possible but in no event later than 7 calendar  days.  The UW HS-IRB will be 
notified in accordance with posted institutional policy. 
Adverse Events:  Serious and Non Serious Adverse events will be recorded, regardless of 
whether or not they are thought to be related to the investigational imaging tracer.  While all 
adverse events will be tabulated and reported in the study final report, serious adverse events will 
be reported in the course of the trial.  Adverse events that meet criteria of a serious adverse event 
listed above will also be recorded and reported. 
The Investigator will inform the IRB of all adverse events attributed to the investigational imaging 
tracer in accordance with posted institutional policy. 
8.0 
PRIVACY AND CONFIDENTIALITY PROTECTIONS 
Research procedures will be conducted in private areas and we are only collecting the minimum 
amount of information necessary to conduct the study. No sensitive data (HIV status, illicit drug 
use) will be collected. Identifiable records will only be available to study team members. 
Data are not being shared outside of UW except through publications, in which case the data do 
not identify individual subjects. Study data will be managed by Drs. Barriohlet and Sadowski. Data 
will not be placed on unencrypted laptop computers. Coded electronic data will be kept on the 
Obstetrics and Gynecology and Radiology Department secure network drives. A separate file 
linking codes to subject identity will be kept in the same manner, in a folder separate from study 
data. At the end of 7 years study data will be de-identified by destroying the link to identifiable 


20 
 
information. Until that time data will remain coded and the file linking codes to subject identity kept 
as well.  
All imaging will be performed for research purposes only and will be given a unique study number 
that cannot be linked to the patients’ medical records in any way. Imaging research images will 
be stored on PACS under this study number only. The investigators will have access to the 
patients’ electronic medical records that are relevant to this study. Study records will be kept for 
seven years. Study data will be managed by the PI and co-PI. 
Subject’s identifiable information will be linked to a study code.  The study code will be used to 
identify the subject and research images.  Research images may be used in scientific 
presentations, but all images will be de-identified. The data will be stored on the Principal 
Investigator’s (PI or co-PI) password protected computer in her locked office. The code will be 
stored separate from the data on the PI’s computer in her locked office.   
9.0 
DATA AND SAFETY MONITORING 
Safety monitoring of research protocols investigating novel PET tracers utilize a combination of 
tools. These are framed to provide adequate clinical trial oversight ensuring that the research 
team is complying with the conditions of IRB approval and FDA requirements. The tools enable 
frequent evaluations of study-related activities, identification of deviations or noncompliance with 
the conduct of the study or protocol, review of adverse events tracking and reporting, and review 
of drug production and accountability. 
 
These tools include: 
• 
Study visit checklists – Research Coordinators use study visit checklists to ensure that all 
study required procedures and processes are met before, during and after the subject has 
been seen. Items listed on these checklists include informed consent obtained, consent 
questions answered (and by whom), vitals recorded, medications reviewed, MR safety 
form, etc. These checklists are reviewed by the study coordinator and are signed off for 
each study subject by the coordinator monitoring the study to ensure that protocols are 
followed accurately and include limited variance from protocol.  
 
• 
Safety monitoring – The safety monitoring of subjects enrolled in the research includes 
both internal and external safety checks governing the administration of 18F-DCFPyL. 
Internal monitoring is performed by co-investigators and external monitoring by a team of 
four physicians with the appropriate broad clinical and technical. The internal monitoring 
plan includes a brief review of each subject visit after it occurs.  In this regard, the study 
team will discuss data quality, 18F-DCFPyL production and administration, and subject 
compliance and tolerance of research procedures.  
 
The external monitoring plan will be coordinated by the Department of Radiology Medical 
Imaging Research Support (MIRS) administrative team.  MIRS is a working group that 
provides investigators with the support needed to conduct clinical research that uses 
imaging as an outcome measure.  Members include a core administrative group 


21 
 
(physicians, scientists, imaging modality managers, regulatory and administrative support) 
and ad hoc members recruited when their expertise is required for the review/monitoring 
of a research project. MIRS administrative team in addition to a 4-person committee of 
physicians/scientists will meet annually with representatives from the research team, to 
discuss research progress, AE/SAE reports, as well as other data reports compiled by the 
study team.  If an AE/SAE occurs, an ad hoc committee meeting will be organized to 
discuss whether the event is considered serious, whether it can be attributed to research 
procedures, whether it constitutes non-compliance on the part of the study team, and the 
plan for resolution and a future remediation plan. 
 
As part of this plan, the monitor(s) will verify that:  
• 
The rights and well-being of human subjects are protected  
• 
Reported study data are accurate, complete, and verifiable from source documents  
• 
The conduct of the study is in compliance with the currently approved protocol, 
GCPs, applicable regulatory requirements, and guidelines for clinical research 
studies at the University of Wisconsin-Madison and its affiliates  
 
10.0 
STATISTICAL CONSIDERATIONS 
The goals of this study are to 1) record the normal distribution of PSMA in the body, 2) record the 
frequency that the normal fallopian tubes and ovarian are seen on high resolution MR imaging, 
3) record the distribution of PSMA in cancer tissue, and 4) estimate the sensitivity, specificity, and 
accuracy of PSMA PET and MR imaging.  
12 healthy controls and 40 subjects with known gynecologic cancer will be enrolled in this pilot 
study. With final IHC staining as the “gold standard” in detection of cancer, we will estimate the 
sensitivity, specificity, and accuracy of PSMA PET and MR imaging. The sample size was chosen 
based on logistical and financial considerations. The table below shows the precision with which 
we will be able to estimate the sensitivity and specificity of PSMA PET and MR imaging. 
Sensitivity/Specificity  
Width of 95% CI 
65% 
31.1% 
70% 
29.9% 
72.5% 
29.3% 
75% 
28.5% 
77.5% 
27.7% 
80% 
26.5% 
82.5% 
25.5% 
85% 
24.1% 
 
Based on this pilot study, we plan to pursue further evaluation in larger, more appropriately 
powered studies if sensitivity and specificity are at least 80%.  


22 
 
11.0 
DRUG FORMULATION AND PROCUREMENT 
Investigation Product 
The 
investigational 
product 
will 
be 
obtained 
from 
the 
University 
of 
Wisconsin 
Radiopharmaceutical Production Facility (RPF).  The RPF is located in the Wisconsin Institute for 
Medical Research Building.  The FDA IND for this protocol will be cross-filed with the current 
Johns Hopkins University IND for 18F-DCFPyL, IND # 121064 to reference the Pharmacology 
and Toxicology, dosimetry, and Previous Human Experience sections of that IND. 
 
18F-DCFPyL is eluted with 1 mL of ethanol followed by 10 mL of 0.9% sodium chloride, via a 
sterilizing 0.22μ filter into a sterile vial containing 4 mL 0.9% sodium chloride.  Test 
radiopharmaceutical will be administered intravenously via slow I.V. push.  The maximum 
mass dose of the ligand corresponding to the <9 mCi dose of 18F-DCFPyL will be less than 
3.98 µg per administration, although the actual dose will be significantly less depending on the 
specific activity achieved during each radiosynthesis run.  The lowest limit for specific-activity 
(SA) we will use at the time of injection is 1000 mCi/µmole, although the validation and phase 
I study radiosynthesis SA was significantly higher than 1000 mCi/µmole. 
 
Preclinical Toxicology 


23 
 
A toxicity report “14-Day Study to Determine Toxicity of DCFPyL from a Single 
IV Dose in Sprague Dawley Rats” was prepared by SoBran Inc. (Study No. SB-MP-001).  The 
following summary is taken from that report. 
 
The purpose of this study was to evaluate the toxicity of DCFPyL three and fifteen days 
following a single intravenous dose in rats.  This study consisted of two test article treatment 
groups of ten male and female Sprague-Dawley rats per group dosed with DCFPyL at 0.1 and 
0.5 mg/kg.  An additional group of ten males and ten females received the vehicle, 5% 
Dextrose, and served as the control.  All rats received a dose volume of 5 mL/kg.  The rats 
were dosed intravenously once on Study Day 1.  Five male and five female rats from each 
group were bled on Study Day 3 and the remaining rats were bled on Study Day 15.  All 
animals were euthanized and necropsied following blood collection.  Parameters evaluated for 
test article effect included survival, clinical observations, body weight, body weight gain, 
clinical pathology, gross pathology, organ weights, and microscopic pathology. 
 
All rats survived to the scheduled termination and remained bright, alert and responsive during 
the study.  No abnormal findings were indicated during cageside or hands-on observations.  
One female rat treated with the vehicle control and one female rat treated with 0.1 mg/kg 
DCFPyL lost weight between Days 8 and 15. All rats treated with 5% Dextrose or DCFPyL 
gained weight during the course of the study.  There were no treatment related changes seen 
in the hematology, coagulation, or clinical chemistry data.  Organ weights showed some 
variance but microscopic findings in the Day 3 and Day 15 rats were considered incidental and 
not directly related to the test article.  Under the conditions of this study, there were no 
treatment related findings in Sprague Dawley rats three or fifteen days after a single 
intravenous dose of DCFPyL at 0.1 mg/kg and 0.5 mg/kg.  
 
 
 


24 
 
18F-DCFPyL was assessed for its ex-vivo pharmacokinetics in non-obese diabetic severe-
combined immunodeficient (NOD-SCID) mice bearing both PSMA positive PC3-PIP and 
PSMA negative PC3-flu xenografts.  Table below shows the percent injected dose per gram 
of tissue (%ID/g) of 18F-DCFPyL activity in selected organs. 
 
18F-DCFPyL PSMA-dependent uptake within PSMA positive PC3 PIP xenografts, reaching a 
value of 46.7 ± 5.8%ID/g at 30 minutes post-injection (p.i.), which decreased by only about 
10% over the ensuing 4 hours.  At 60 minutes p.i. the kidney, liver, and spleen displayed the 
highest uptake.  By that time, the urinary bladder also showed relatively high uptake.  However, 
that uptake includes excretion at all-time points.  Rapid clearance from the kidneys was shown, 
decreasing from 74.1 ± 6.6%ID/g at 30 minutes to 7.4 ± 0.9%ID/g at 4 hours.  The relatively 
high values noted in kidney are partially due to high expression of PSMA within proximal renal 
tubules.  The ratio of uptake within PSMA positive PIP to PSMA negative flu tumors ranged 
from 40:1 to more than 1,000:1 over the 4-hour time period of the study.  A possible 
explanation for that increased tumor uptake of radiochemical over time could be due to ligand-
mediated PSMA internalization within tumor cells.  Less retention in kidney relative to tumor 
over time could be due to a lower degree of internalization in this (normal) tissue and/or 
different metabolism of 18F-DCFPyL, which does not promote retention of radiochemical in 
kidney.  Relatively low bone uptake (<1% ID/g at all-time points) suggests little metabolic 
defluorination of 18F-DCFPyL.  The total effective dose for 333 MBq (9 mCi) of 18F-DCFPyL 
was calculated to be 5.93 mGy (0.593 rem) based on animal models. 
 
Initial Phase I Study Adverse Events: 
An initial phase I study of the biodistribution and dosimetry of 18F-DCFPyL found that in nine 
patients there were no severe adverse events. One patient reported two adverse events that 
were classified as unlikely to be attributable to the radiotracer (mild headache and mild nose 
bleed, both of which resolved without treatment and were considered Grade I by the National 
Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0). 
Another participant experienced a decrease in platelet count on routine assessment during 
the post-imaging follow up which, at the time of publication, had not resolved but which was 
attributed to the participant starting treatment for prostate cancer. This was also a NCI CTCAE 
Grade I adverse event.  There were no radiotracer-related adverse events with monitored 
heart rate or blood pressure. 
 
Human dosimetry: 18F-DCFPyL human dosimetry reported in Risks/Benefits section. 
 
 


25 
 
12.0 
REFERENCES 
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Barbieri, C.E., et al., The Emergence of Precision Urologic Oncology: A Collaborative 
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Cho, Steve, et al., Biodistribution, Tumor Detection, and Radiation Dosimetry of 18F-
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