A PrOspective Phase 2/3 Multi-Center Study of 18F-DCFPyL PET/CT Imaging in Patients With PRostate Cancer: Examination of Diagnostic AccuracY (OSPREY)
Phase: PHASE2
Conditions: Prostate Cancer
Sponsor: Progenics Pharmaceuticals, Inc.

Clinical Protocol:  PyL-2301 
18F-DCFPyL 
Amendment 2: 06 Nov 2017 
Page 1 
CLINICAL STUDY PROTOCOL 
Study Number: 
PyL 2301 
Study Title: 
A PrOspective Phase 2/3 Multi-Center Study of 18F-DCFPyL PET/CT 
Imaging in Patients with PRostate Cancer: Examination of Diagnostic 
AccuracY (OSPREY) 
Product Name: 
18F-DCFPyL INJECTION (PyL) 
IND Number 
129,952 
Sponsor: 
Progenics Pharmaceuticals, Inc. 
One World Trade Center 
47th Floor, Suite J 
New York, NY 10007   
(646) 975-2500
Protocol Version 
Original:  July 12, 2016 
Amendment 1: September 16, 2016 
Amendment 2: November 6, 2017
NCT02981368 
Confidentiality Statement 
The confidential information in this document is provided to you as an investigator or consultant for review by 
you, your staff, and the applicable Institutional Review Board/Independent Ethics committee.  Your acceptance 
of this document constitutes agreement that you will not disclose the information contained herein to others 
without prior written authorization from Progenics Pharmaceuticals, Inc. 

Clinical Protocol:  PyL-2301 
18F-DCFPyL 
Amendment 2: 06 Nov 2017 
Page 2 
INVESTIGATOR’S AGREEMENT 
I acknowledge that I have read the attached protocol and agree that it contains all information 
necessary to conduct the study and agree to conduct the study as outlined within. 
I agree to comply with all stated provisions, including but not limited to regulations/guidelines 
relevant to the conduct of human trials, as set forth in Title 21 of the Code of Federal 
Regulations (CFR), and Good Clinical Practices as set forth by International Conference on 
Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use 
(ICH).   
I will not initiate the study until I have obtained written approval from the appropriate 
Institutional Review Board (IRB)/Independent Ethics Committee (IEC).  I will obtain written 
informed consent from all study participants prior to performing any screening procedures. 
I agree to maintain the confidentiality of all information received or developed in connection 
with this protocol.  I understand and acknowledge that confidential information includes, but is 
not limited to, (i) the study protocol, (ii) the data derived from the study, and (iii) my impressions 
of the progress or results of the study.  I further agree that I will not use such Confidential 
Information for any purpose other than the evaluation or conduct of the clinical investigation.   
I certify that I have not been disqualified by any regulatory authority or otherwise disqualified 
from serving as a principal investigator.  I also agree that in the event I become debarred, I shall 
immediately cease all activities relating to the study. 
I am not presently, nor will I be during the term of the study, a consultant or advisor to any 
division of any financial or securities firm.  
I understand that my signature on a case report form indicates that the data therein have been 
reviewed and are deemed to be complete, accurate, and acceptable to me. 
Printed Name of Principal Investigator 
Signature of Principal Investigator 
Date 

Clinical Protocol:  PyL-2301 
18F-DCFPyL 
Amendment 2: 06 Nov 2017 
Page 4 
PROCEDURES IN CASE OF EMERGENCY 
Table 1: 
Emergency Contact Information 
Role in Study 
Name 
E-mail and Telephone
Number
Clinical Project Manager 
Clinical Study Leader 
Responsible Physician 

Clinical Protocol:  PyL-2301 
18F-DCFPyL 
Amendment 2: 06 Nov 2017 
Page 5 
1.
TABLE OF CONTENTS
2.
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS...............................9 
3.
INTRODUCTION ......................................................................................................12 
3.1. 
Background Information .............................................................................................12 
3.2. 
Rationale for Developing Prostate Cancer Imaging Agents .......................................12 
3.3. 
Targeting PSMA for Prostate Cancer Detection ........................................................13 
3.4. 
18F-DCFPyL ................................................................................................................15 
3.5. 
Rationale for Dose Selection ......................................................................................16 
4.
TRIAL OBJECTIVES AND PURPOSE ....................................................................17 
4.1. 
Primary Objective .......................................................................................................17 
4.2. 
Secondary Objectives .................................................................................................17 
4.3. 
Exploratory Objectives ...............................................................................................17 
5.
TRIAL ENDPOINTS .................................................................................................18 
5.1. 
Primary Endpoints ......................................................................................................18 
5.2. 
Secondary Endpoints ..................................................................................................18 
5.3. 
Exploratory Endpoints ................................................................................................18 
6.
INVESTIGATIONAL PLAN .....................................................................................19 
6.1. 
Overall Study Design ..................................................................................................19 
6.2. 
Number of Subjects ....................................................................................................19 
6.3. 
Treatment Assignment ................................................................................................19 
6.4. 
Dose Adjustment Criteria ...........................................................................................20 
6.5. 
Study Duration ............................................................................................................20 
6.6. 
Safety Monitoring .......................................................................................................20 
6.7. 
Criteria for Study Termination ...................................................................................20 
7.
SELECTION AND WITHDRAWAL OF SUBJECTS ..............................................23 
7.1. 
Subject Inclusion Criteria ...........................................................................................23 
7.2. 
Subject Exclusion Criteria ..........................................................................................23 
7.3. 
Subject Withdrawal Criteria .......................................................................................24 
8.
TREATMENT OF SUBJECTS ..................................................................................24 
8.1. 
Description of Study Drug ..........................................................................................24 
8.2. 
Concomitant Medications and Procedures .................................................................25 

Clinical Protocol:  PyL-2301 
18F-DCFPyL 
Amendment 2: 06 Nov 2017 
Page 6 
8.3. 
Treatment Compliance ................................................................................................25 
8.4. 
Randomization and Blinding ......................................................................................25 
9.
STUDY DRUG MATERIALS AND MANAGEMENT ...........................................25 
9.1. 
Study Drug ..................................................................................................................25 
9.2. 
Restrictions .................................................................................................................25 
9.2.1. 
Food and Fluid Intake .................................................................................................25 
9.2.2. 
Activity .......................................................................................................................26 
9.3. 
Study Drug Packaging and Labeling ..........................................................................26 
9.4. 
Study Drug Storage .....................................................................................................26 
9.5. 
Study Drug Preparation ..............................................................................................26 
9.6. 
Administration ............................................................................................................26 
9.7. 
Study Drug Accountability .........................................................................................27 
9.8. 
Study Drug Handling and Disposal ............................................................................27 
10.
ASSESSMENT OF EFFICACY ................................................................................28 
10.1. 
Image Acquisition .......................................................................................................28 
10.1.1. 
18F-DCFPyL PET/CT (all cohorts) .............................................................................28 
10.1.2. 
Bone Scan (all cohorts) ...............................................................................................28 
10.1.3. 
CT or MRI (all cohorts) ..............................................................................................28 
10.1.4. 
Biopsy Guided Imaging (cohort B only) ....................................................................28 
10.2. 
Image Interpretation ....................................................................................................28 
10.3. 
Prostatectomy and Lymphadenectomy .......................................................................29 
10.4. 
Interventional Radiology ............................................................................................29 
10.5. 
Biopsy and Surgical Pathology ...................................................................................29 
10.6. 
Pharmacokinetics ........................................................................................................29 
11.
ASSESSMENT OF SAFETY .....................................................................................31 
11.1. 
Safety Parameters .......................................................................................................31 
11.1.1. 
Demographic/Medical History ...................................................................................31 
11.1.2. 
Vital Signs ..................................................................................................................31 
11.1.3. 
Weight and Height ......................................................................................................31 
11.1.4. 
Electrocardiogram (ECG) ...........................................................................................31 
11.1.5. 
Laboratory Assessments .............................................................................................31 
11.1.5.1. 
Hematology, Blood Chemistry, PSA and Testosterone..............................................31 

Clinical Protocol:  PyL-2301 
18F-DCFPyL 
Amendment 2: 06 Nov 2017 
Page 7 
11.2. 
Adverse and Serious Adverse Events .........................................................................32 
11.2.1. 
Definition of Adverse Events .....................................................................................32 
11.2.1.1. 
Adverse Event (AE) ....................................................................................................32 
11.2.1.2. 
Serious Adverse Event (SAE) ....................................................................................32 
11.3. 
Relationship to Study Drug ........................................................................................33 
11.4. 
Recording Adverse Events .........................................................................................33 
11.5. 
Reporting Serious Adverse Events .............................................................................34 
12.
STATISTICS ..............................................................................................................34 
12.1. 
Sample Size ................................................................................................................34 
12.2. 
Analysis Populations ..................................................................................................35 
12.2.1. 
Screened Subjects .......................................................................................................35 
12.2.2. 
Safety Set ....................................................................................................................35 
12.2.3. 
Evaluable Set ..............................................................................................................35 
12.2.4. 
Per Protocol Set ..........................................................................................................36 
12.2.5. 
PK Evaluable Set ........................................................................................................36 
12.3. 
Endpoints and Derivations ..........................................................................................36 
12.3.1. 
Sensitivity, Specificity, PPV, and NPV ......................................................................36 
12.3.2. 
Lesions Per Subject .....................................................................................................37 
12.3.3. 
Change from Baseline .................................................................................................37 
12.3.4. 
Pre-Treatment and Concomitant Medications ............................................................37 
12.3.5. 
Treatment-Emergent Adverse Events .........................................................................37 
12.4. 
Missing Data ...............................................................................................................37 
12.5. 
Analyses ......................................................................................................................37 
12.5.1. 
Subject Characteristics ................................................................................................37 
12.5.2. 
Efficacy Analysis ........................................................................................................38 
12.5.2.1. 
Primary Endpoint ........................................................................................................38 
12.5.2.2. 
Secondary Endpoints ..................................................................................................38 
12.5.2.3. 
Exploratory Analyses ..................................................................................................39 
12.5.3. 
Safety ..........................................................................................................................39 
12.5.3.1. 
Exposure .....................................................................................................................39 
12.5.3.2. 
Adverse Events ...........................................................................................................40 
12.5.3.3. 
Clinical Laboratory .....................................................................................................40 

Clinical Protocol:  PyL-2301 
18F-DCFPyL 
Amendment 2: 06 Nov 2017 
Page 8 
12.5.3.4. 
ECG ............................................................................................................................40 
12.5.3.5. 
Vital Signs ..................................................................................................................40 
12.5.4. 
Pharmacokinetics ........................................................................................................40 
13.
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS.........................................40 
13.1. 
Study Monitoring ........................................................................................................40 
13.2. 
Audits and Inspections ................................................................................................41 
14.
ETHICS ......................................................................................................................42 
14.1. 
Good Clinical Practice (GCP), Laws and Regulations ...............................................42 
14.2. 
Institutional Review Board (IRB) or Independent Ethics Committee (IEC) 
Approval .....................................................................................................................42 
14.3. 
Written Informed Consent ..........................................................................................42 
14.4. 
Subject Confidentiality ...............................................................................................43 
14.5. 
Financial Disclosure ...................................................................................................43 
15.
DATA HANDLING AND RECORDKEEPING .......................................................43 
15.1. 
Case Report Forms and Study Records ......................................................................43 
15.2. 
Inspection of Records .................................................................................................43 
15.3. 
Retention of Records ..................................................................................................43 
16.
PUBLICATION AND DISCLOSURE POLICY .......................................................44 
17.
REFERENCES ...........................................................................................................45 
LIST OF TABLES 
Table 1: 
Emergency Contact Information ...................................................................................4 
Table 2: 
Abbreviations and Specialist Terms .............................................................................9 
Table 3: 
Schedule of Assessments ............................................................................................21 
Table 4: 
Investigational Product ...............................................................................................24 
Table 5: 
PK Sampling & Imaging Timepoints .........................................................................30 
Table 6: 
Clinical Laboratory Tests ...........................................................................................32 
Table 7: 
Classification of 18F-DCFPyL Imaging Result and Histopathology Result for 
Cohorts A and B Separately .......................................................................................36 
LIST OF FIGURES 
Figure 1: 
Study Schema .............................................................................................................20 

Clinical Protocol:  PyL-2301 
18F-DCFPyL 
Amendment 2: 06 Nov 2017 
Page 9 
2.
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS
The following abbreviations and specialist terms are used in this study protocol. 
Table 2: 
Abbreviations and Specialist Terms  
Abbreviation or Specialist Term 
Explanation 
AE 
adverse event 
ALT 
alanine aminotransferase (SGPT) 
AST 
aspartate aminotransferase (SGOT) 
AUC 
area under the time-concentration curve 
BP 
blood pressure 
BUD 
beyond use date 
BUN 
blood urea nitrogen 
CBC 
complete blood count 
CFR 
Code of Federal Regulations 
CL 
total body clearance 
CMP 
comprehensive metabolic panel 
Cmax
maximum (peak) serum concentration 
CRF 
case report form 
CT 
computed tomography 
DMC 
Data Monitoring Committee 
DoB 
date of birth 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
EOS 
End of Synthesis 
FDA 
Food and Drug Administration 
18F 
Fluorine-18 
FDG 
Fluorodeoxyglucose 
68Ga 
Gallium-68 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
hr 
Hour(s) 
HR 
Heart Rate 

Clinical Protocol:  PyL-2301 
18F-DCFPyL 
Amendment 2: 06 Nov 2017 
Page 10 
Table 2: 
Abbreviations and Specialist Terms 
Abbreviation or Specialist Term 
Explanation 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
IEC 
Independent Ethics Committee 
IND 
Investigational New Drug 
IRB 
Institutional Review Board 
IV 
Intravenous  
JHU 
Johns Hopkins University 
kg 
Kilogram 
m 
Minute/Meter 
mAb 
Monoclonal Antibody 
MBq 
MegaBequerel 
mCi 
MilliCurie 
MDP 
methylene diphosphonate bone scan 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg 
Milligram 
mL 
Milliliter 
MRI 
Magnetic Resonance Imaging 
MRT 
Mean Residence Time 
mSv 
millisievert 
N/A 
not applicable 
NCCN 
National Comprehensive Cancer Network 
NCI 
National Cancer Institute 
CTCAE 
Common Terminology Criteria for Adverse Events 
ng 
nanogram 
nM 
nanometer 
NOAEL 
No Observed Adverse Effect Level 
NPV 
negative predictive value 
PET/CT 
positron emission tomography–computed tomography 
PI 
Principal Investigator 
PK 
pharmacokinetics 

Clinical Protocol:  PyL-2301 
18F-DCFPyL 
Amendment 2: 06 Nov 2017 
Page 11 
Table 2: 
Abbreviations and Specialist Terms 
Abbreviation or Specialist Term 
Explanation 
PLND 
Pelvic lymph node dissection 
PPV 
Positive Predictive Value 
PSA 
Prostate Specific Antigen 
PSMA 
Prostate-Specific Membrane Antigen 
PT 
Preferred Term 
RBC 
Red Blood Cell count 
RCC 
Renal cell carcinoma 
RP 
radical prostatectomy 
RR 
respiratory rate 
SAE 
Serious Adverse Event 
SAP 
statistical analysis plan 
SD 
Standard deviation 
SoC/SOC 
Standard of Care/System Organ Class 
SOP 
Standard Operating Procedures 
SUVmax 
Maximum Standardized Uptake Value 
SUVpeak 
Peak standardized uptake value 
SUVr 
ratio to reference tissue standardized uptake value 
TIAC 
Time-Integrated Activity coefficients 
US 
United States 
Vss 
Volume of Distribution at Steady State 
WBC 
White Blood Cell count 

Clinical Protocol:  PyL-2301 
18F-DCFPyL 
Amendment 2: 06 Nov 2017 
Page 12 
3.
INTRODUCTION
3.1. 
Background Information
Prostate cancer is the most common cancer among men in the United States (US) with an 
estimated number of new cases of 161,360 annually; it also represents the second most common 
cause of cancer-related death in men.1  The vast majority of men dying of prostate cancer 
succumb to metastatic, recurrent disease.  Thus imaging modalities that can detect, monitor, and 
restage residual, recurrent locoregional disease, and metastatic disease are highly desirable.  
Conventional anatomic and functional imaging including contrast-enhanced computed 
tomography (CT), [99mTc] methylene diphosphonate (MDP) bone scan, ultrasound, or magnetic 
resonance imaging (MRI) may not be sufficiently sensitive and specific for detection of prostate 
cancer lesions.2-5 
Tumors typically exhibit abnormally high metabolism and this mechanism has been exploited for 
imaging cancers.  Positron emission tomography (PET) employing 2-deoxy-2-[18F]fluoro-D-
glucose (FDG PET), the clinical standard for a number of cancers, has demonstrated mixed 
results in imaging prostate cancer.6-9  Other tumor metabolism-based approaches tested in 
prostate cancer (and other cancers) are the use of labeled choline to take advantage of the 
increased expression of choline kinase (ChKα) in tumor cells10, or increased uptake of amino 
acids such as methionine or leucine.  11C choline was approved by FDA in 2012; however, the 
sensitivity of 11C choline tends to be limited in extraprostatic lesions.11-14  Most recently, 
synthetic L-leucine analog trans‐1‐amino‐3‐18F‐fluoro‐cyclobutane carboxylic acid (18F‐FACBC; 
Axumin®) was approved for use in men with suspected recurrence of prostate cancer. 
A number of new, targeted PET tracers have been introduced for imaging prostate cancer.15-20  
Proving particularly effective are low-molecular-weight agents that bind to the prostate-specific 
membrane antigen (PSMA), which is highly expressed in castration-resistant, metastatic prostate 
cancer.21,22,23  A novel, high specific activity, highly selective, low-molecular weight PSMA-
targeted PET radiotracer, 18F-DCFPyL, is currently being investigated as an imaging agent for 
prostate cancer at Johns Hopkins University School of Medicine (JHU).  The purpose of the 
current study is to further the clinical development of 18F-DCFPyL to support marketing 
approval. 
3.2. 
Rationale for Developing Prostate Cancer Imaging Agents 
Prostate cancer is a significant public health problem affecting more than 2.3 million men in the 
US and another 4 million in Europe.  Annually, nearly 161,360 new cases of prostate cancer are 
diagnosed in the US, coupled with approximately 400,000 newly diagnosed cases in Europe.1,24  
It is estimated that the disease will affect one in seven men in their lifetimes, leading to 
approximately 293,000 deaths per year in developed countries worldwide.25  The mortality from 
the disease is second only to lung cancer in men.1  An estimated $8 billion is currently spent 
annually in the US on surgery, radiation, drug therapy and minimally invasive treatments.26 
Several imaging modalities are currently employed for the diagnosis, staging and prognosis of 
prostate cancer metastases.  Conventional cross-sectional imaging with CT and MRI rely on 
anatomical changes (lesions >1 cm), often resulting in missed lymph node metastases and low 

Clinical Protocol:  PyL-2301 
18F-DCFPyL 
Amendment 2: 06 Nov 2017 
Page 13 
sensitivity.  Nodal enlargement of metastases occurs relatively late in the progression of prostate 
cancer and neither CT nor MRI are effective at detecting the often microscopic lymph node 
metastases at the earliest stages of disease progression.  Additionally, nodal enlargement can also 
be caused by infection or inflammation, thereby reducing the specificity.  Meta-analyses of 24 
published studies revealed that CT and MRI performed equally poorly in the detection of lymph 
node metastases from prostate cancer.  Results of pooled sensitivity and specificity were 42% 
and 82%, respectively, for CT and 39% and 82%, respectively, for MRI.  Thus, the reliance on 
either CT or MRI may misrepresent the patient’s true status regarding nodal metastases, and 
misdirect the therapeutic strategies offered to the patient.27  Radionuclide bone scans are 
commonly used for monitoring bone metastases.  However, as bone scans detect tissue 
remodeling, as opposed to tumor burden, false positives can be caused by inflammation, previous 
bone injuries, and arthritis, especially in older men.28  Therefore, new agents that will detect and 
localize the primary tumor, as well as small metastatic lesions, with high sensitivity and 
specificity are essential to more accurately diagnose and stage the disease, and monitor therapy. 
3.3. 
Targeting PSMA for Prostate Cancer Detection 
Prostate-specific membrane antigen (PSMA), also known as folate hydrolase I (FOLH1) or 
glutamate carboxypeptidase II (GCPII), is a trans-membrane, 750-amino acid type II 
glycoprotein primarily expressed in normal human prostate epithelium at very low levels, if at 
all, but is upregulated in prostate cancer, including metastatic disease.  PSMA is a unique 
exopeptidase with reactivity toward poly-gamma-glutamated folates that is capable of 
sequentially removing the poly-gamma-glutamyl termini.29,30  Since PSMA is expressed by 
virtually all prostate cancers and its expression is further increased in poorly differentiated, 
metastatic and hormone-refractory prostate carcinomas, it is a very attractive target for 
developing agents for the diagnosis and staging of this disease.31,32,33  In addition to high 
expression in malignant prostatic tissue and being directly related to tumor aggressiveness,34 
PSMA has also been detected in renal proximal tubules, in cells of the intestinal brush border 
membrane, in rare cells in the colonic crypts, in brain, salivary glands,23,31,35,36 and in the 
neovasculature of nonprostatic solid carcinomas (e.g., renal cell, breast, colon, pancreas, 
melanoma, and lung carcinoma).21 
A radiolabeled anti-PSMA monoclonal antibody (mAb) 7E11, marketed as Indium 111 
ProstaScint® (capromab pendetide) is currently being used to detect prostate cancer nodal 
metastasis and recurrence.  ProstaScint was first approved for marketing by the FDA in 1996, 
and while still available today, it is rarely used in practice due to a number of logistical and 
clinical limitations.  Furthermore, ProstaScint targets the intracellular domain of PSMA and is 
therefore thought to bind mostly necrotic portions of the prostate tumor.32 
More recently, radiolabeled monoclonal antibodies that bind to the extracellular domain of 
PSMA have been developed and have been shown to accumulate in PSMA-positive prostate 
tumors in animals.30  Early promising results in man from various phase 1 and 2 trials have 
utilized PSMA as a therapeutic target.37,38  While monoclonal antibodies hold promise for tumor 
detection and therapy, there has been relatively limited clinical success outside of hematological 
cancers due to their low permeability in solid tumors and slow clearance from the circulating 
blood pool.  Smaller molecular weight compounds with higher permeability into solid tumors are 
likely to provide a distinct and definitive advantage in achieving higher percent uptake per gram 

Clinical Protocol:  PyL-2301 
18F-DCFPyL 
Amendment 2: 06 Nov 2017 
Page 14 
of tumor tissue and a high percentage of specific binding.  Small molecules are also expected to 
have improved blood clearance and tissue distribution in normal tissues compared with 
antibodies, thus enhancing the target-to-background and thereby making lesion detection more 
conspicuous. 
In the past few years, a number of investigational PSMA-targeted small molecules have been 
synthesized and labeled with various radioisotopes to be tested for use as imaging agents for 
prostate cancer.  A SPECT agent, 99mTc-MIP-1404, is currently in phase 3 testing for the 
detection of clinically significant prostate cancer in patients with low grade disease.39,40  PET 
imaging agents, such as 124I-MIP-1095, 18F-DCFCBC, 18F-DCFPyL, and 68Ga-HBED-CC, have 
also generated much interest for their potential use in detecting metastatic prostate cancer.  68Ga-
HBED-CC (68Ga-PSMA) has been broadly studied in the clinical setting at academic centers.  In 
a retrospective analysis of patients with high-risk localized disease prior to radical 
prostatectomy, 68Ga-PSMA PET/CT imaging showed a sensitivity of approximately 93% for 
intraprostatic lesions and 33% for regional lymph node metastases.  Specificity, positive and 
predictive values for lymph nodes were 100%, 100% and 69%, respectively.41  A retrospective 
evaluation of data from 68Ga-PSMA PET/CT imaging in patients with biochemical recurrence of 
prostate cancer showed high detection rates, even in patients with low (0.2 to <0.5 ng/ml) PSA 
(58%).42  Studies have also been conducted to compare 68Ga-PSMA PET/CT and 18F-choline 
PET/CT imaging in prostate cancer.  In patients with recurrent prostate cancer scheduled to 
undergo salvage lymphadenectomy (thus providing histopathology as the truth standard), 68Ga-
PSMA PET/CT showed better performance than 18F-choline PET/CT with a significantly higher 
negative predictive value (NPV) and accuracy for the detection of locoregional recurrent and/or 
metastatic lesions prior to salvage lymphadenectomy, with sensitivity of 71% vs 87%, specificity 
of 87% vs. 93%, and accuracy of 83% vs 92%, respectively.43  In patients with biochemical 
recurrence of prostate cancer with a negative [18F]-choline PET/CT, 68Ga-PSMA-PET/CT 
identified sites of recurrent disease in 43.8% of the patients with negative F-choline PET/CT 
scans.44  Another study was conducted to compare the detection rate of two PSMA-targeted 
PET/CT imaging agents side-by-side (18F-DCFPyL and 68Ga-PSMA) in patients with recurrence 
of prostate cancer.45  The results showed that 18F-DCFPyL PET/CT provided high image quality 
and visualized small prostate lesions with excellent sensitivity.  Furthermore, F-18 tracers in 
general offer important advantages over Ga-68 tracers, including higher production capacity 
from the use of a cyclotron as opposed to depending on the supply from Ga generators, and 
higher image resolution due to the intrinsic physical properties of F-18 (lower positron emission 
energy compared to Ga-68).  Thus, overall, 18F-DCFPyL PET/CT may represent a promising 
alternative to 68Ga-PSMA PET/CT for imaging prostate cancer. 
PyL is a radiolabeled PSMA-targeted small molecule discovered at JHU that was in-licensed by 
Progenics in 2015.  It is currently being studied in phase 1 and phase 2 clinical trials under 
JHU’s IND 121,064 for the detection of primary and metastatic prostate cancer.  In collaboration 
with JHU, Progenics plans to complete the clinical development program of PyL and eventually 
seek FDA approval of PyL for the detection of prostate cancer. 

Clinical Protocol:  PyL-2301 
18F-DCFPyL 
Amendment 2: 06 Nov 2017 
Page 15 
3.4. 
18F-DCFPyL 
18F-DCFPyL Injection is a radiolabeled small molecule that binds to the extracellular domain of 
PSMA with high affinity.  PSMA is a transmembrane glycoprotein expressed by virtually all 
prostate cancers, and its expression is further increased in metastatic and hormone-refractory 
prostate carcinomas, which makes it a useful target for developing agents for the diagnosis and 
staging of prostate cancer. 
The nonclinical studies conducted with DCFPyL and 18F-DCFPyL included biochemical activity, 
biodistribution in xenograft mice, small animal PET imaging, and a single dose IV toxicology 
study in rats.  Data from enzyme inhibition assay showed that DCFPyL binds competitively to 
PSMA expressing LNCaP cells with a Ki of 1.1 nM.  Studies in PSMA positive tumor bearing 
nude mice demonstrated significant tumor uptake and retention, coupled with a rapid clearance 
from non-target organs to provide support for the further development of 18F-DCFPyL as a 
radiopharmaceutical for detection and localization prostate cancer in man.  Results from a 14-day 
single dose rat toxicology studies with DCFPyL resulted in a no observed adverse effect level 
(NOAEL) of 0.5 mg/kg, the highest dose tested.  The maximum human mass dose of DCFPyL is 
expected to be 4 µg; thus, this represents an estimated safety margin of >1200-fold the human 
equivalent dose. 
Several investigator-initiated clinical studies with 18F-DCFPyL Injection in prostate cancer, as 
well as non-prostate cancer, are currently ongoing at Johns Hopkins University under IND 
121,064.  As of March 2016, 18F-DCFPyL Injection has been administered to a total of 108 
subjects at doses averaging 9 ± 1 mCi per injection.  Preliminary safety and efficacy data from 
two of these studies (J1418, J1545) are currently available. 
Study J1418 is a first in human, phase 1/2 study, conducted to evaluate the radiation dosimetry, 
biodistribution, metabolism, and safety of 18F-DCFPyL Injection with PET/CT imaging in men 
with metastatic prostate cancer.  Once safety was established, the utility of 18FDCFPyL PET/CT 
imaging to detect local, nodal, and/or metastatic prostate cancer was assessed in men with 
advanced prostate cancer.   
Study J1545, a phase 2 single-center, open-label study in men diagnosed with biochemical 
recurrence of prostate cancer.  The study was conducted to evaluate the safety of 18F-DCFPyL 
Injection, to determine the location of putative sites of metastatic disease by 18F-DCFPyL 
PET/CT, to correlate findings on 18F-DCFPyL PET/CT with conventional imaging, and to assess 
treatment response by 18F-DCFPyL PET/CT following six months of standard of care therapy. 
Data from these clinical studies at JHU demonstrate that PET imaging with 18F-DCFPyL 
Injection is feasible and safe.  Biodistribution following administration of 18F-DCFPyL Injection 
and optimal imaging time point were determined and radiation dose used was within limit for 
diagnostic radiotracers for PET.  Physiologic accumulation of 18F-DCFPyL was found to 
correspond to the distribution of PSMA expressing organs.  Accumulation in primary tumor and 
metastatic lesions was very high, suggesting that 18F-DCFPyL Injection can be used to 
prospectively detect residual tumor as well as regional or distance metastases with high 
sensitivity and specificity.   

Clinical Protocol:  PyL-2301 
18F-DCFPyL 
Amendment 2: 06 Nov 2017 
Page 16 
Safety results from all ongoing studies at JHU to date indicate that 18F-DCFPyL Injection is well 
tolerated, with no reported serious adverse events in any of the studies thus far.  A total of 6 
adverse events have been reported, one of which was attributed as possibly related to study drug 
(Grade 1 Headache). 
Progenics has obtained authorization from JHU to reference, and incorporate by reference, the 
data from the phase 1 and phase 2 studies conducted under the JHU IND.  Based on the 
promising results from these clinical studies, Progenics plans to initiate the current phase 2/3 
study (PyL 2301) under a new, separate IND to investigate the safety and efficacy of PyL 
imaging in patients with prostate cancer.  
3.5. 
Rationale for Dose Selection 
Prior to the first-in-human study with PyL (Study J1418) at JHU, human dosimetry was 
extrapolated from a preclinical biodistribution study in xenograft mice.46  The mouse organ 
activity concentrations in %ID/g were converted to the human %ID/ organ by setting the ratio of 
organ %ID/g to whole-body %ID/g in the mouse equal to that in humans and then solving for the 
human %ID/organ.  The adult male phantom organ masses listed in the OLINDA/EXM 1.0 were 
used for the conversion.  The human source organ time-activity curves were fitted using a 
monoexponential function.  Because the biodistribution data were radioactive decay-corrected, 
only the biological removal constants were obtained from the curve fits, and the physical decay 
constant for F-18 was added in obtaining the time-integrated activity coefficients (TIAC).  The 
source organ TIACs in MBq-h/MBq were entered in the OLINDA/EXM 1.0 for the dose 
calculations.  The dynamic voiding bladder model was used to obtain the TIAC for the urinary 
bladder contents.  The whole-body clearance half-life (obtained as the sum of sampled tissues, 
excluding the tumors) was used as the half-life to describe urinary bladder filling.  All 
radioactivity was assumed to be eliminated via the urine.  A one hour voiding interval was 
assumed. 
The urinary bladder wall was projected to be the organ with the highest absorbed dose.  To limit 
the radiation-absorbed dose to the urinary bladder (≤ 50 mGy), the highest human dose is 
estimated to be 8.95 mCi.  As a result, the first-in-human dose used at JHU for obtaining basic 
information regarding the metabolism (including kinetics, distribution, and localization) was 
determined to be ≤9 mCi.  The 9 mCi administered dose of 18F-DCFPyL Injection results in a 
comparable radiation dose to that of other radiotracers used in oncology such as [18F]-FDG. 

Clinical Protocol:  PyL-2301 
18F-DCFPyL 
Amendment 2: 06 Nov 2017 
Page 17 
4.
TRIAL OBJECTIVES AND PURPOSE
4.1. 
Primary Objective
The primary objective of the study is to assess the diagnostic performance of 18F-DCFPyL 
PET/CT imaging to determine the presence or absence of metastatic disease in pre-prostatectomy 
patients with high risk prostate cancer (cohort A)   
4.2. 
Secondary Objectives 
1. To evaluate the safety and tolerability of 18F-DCFPyL
2. To assess the diagnostic performance of 18F-DCFPyL PET/CT imaging to determine the
presence or absence of prostate cancer within sites of metastasis or local recurrence
(cohort B)
3. To determine detection rates of 18F-DCFPyL PET/CT and conventional imaging among
lesion locations (e.g., bone, lymph nodes, soft tissue, prostate gland)
4. To determine positive and negative predictive value (PPV and NPV) of 18F-DCFPyL
PET/CT imaging
5. To determine the pharmacokinetics, biodistribution, and excretion of 18F-DCFPyL
4.3. 
Exploratory Objectives 
1. To assess 18F-DCFPyL uptake among lesion locations (e.g., bone, lymph nodes, soft
tissue, prostate gland)
2. To assess the relationship between 18F-DCFPyL uptake in prostatic and extraprostatic
lesions with baseline PSA and testosterone levels, and Gleason Score at time of radical
prostatectomy
3. To assess the diagnostic performance of 18F-DCFPyL PET/CT imaging to detect prostate
cancer within the prostate gland (cohort A)
4. To assess the  impact of 18F-DCFPyL PET/CT imaging on clinical management plans
5. To determine the PPV of 18F-DCFPyL PET/CT imaging for lesions detected by PET that
are outside the planned surgical template or biopsy site

Clinical Protocol:  PyL-2301 
18F-DCFPyL 
Amendment 2: 06 Nov 2017 
Page 18 
5.
TRIAL ENDPOINTS
5.1. 
Primary Endpoints
1. Specificity of 18F-DCFPyL PET/CT imaging to determine the absence of metastatic
prostate cancer within the pelvic lymph nodes relative to histopathology (cohort A)
2. Sensitivity of 18F-DCFPyL PET/CT imaging to determine the presence of metastatic
prostate cancer within the pelvic lymph nodes relative to histopathology (cohort A)
5.2. 
Secondary Endpoints 
1. Safety and tolerability (Cohorts A and B combined):
a.
Treatment-emergent adverse events
b. Pre- and post-18F-DCFPyL PET/CT lab values, ECGs and vital signs
2. Sensitivity of 18F-DCFPyL PET/CT imaging to detect prostate cancer within sites of
metastasis or local recurrence relative to histopathology (Cohorts B)
3. Comparison of detection rates (Cohorts A and B combined) for lesion counts overall and
by  location (i.e., bone, lymph nodes, soft tissue, prostate gland) between 18F-DCFPyL
and conventional imaging
4. PPV and NPV of 18F-DCFPyL PET/CT imaging (Cohort A) to predict prostate cancer
within the prostate gland and lymph nodes
5. PPV of 18F-DCFPyL PET/CT imaging to predict prostate cancer within sites of local
recurrence and other metastatic lesions (cohort B)
6. Pharmacokinetic parameters [e.g., Cmax, area under the curve (AUC), total clearance
(CL), steady-state volume of distribution (Vss) and mean residence time (MRT)] (subset
of Cohorts A and B combined)
5.3. 
Exploratory Endpoints 
1.
18F-DCFPyL uptake in different lesion locations (i.e., bone, lymph nodes, soft tissue,
prostate gland) as defined by SUVpeak, SUVmax, SUVr results derived from central
readers, compared to histopathology (cohorts A and B)
2. To assess the relationship between SUVpeak, SUVmax and SUVr in prostatic and
extraprostatic lesions with each of the following: baseline PSA, baseline testosterone
level, and Gleason Score at time of radical prostatectomy
3. Sensitivity and specificity of 18F-DCFPyL PET/CT imaging to detect prostate cancer
within the prostate gland relative to histopathology (cohort A)
4. Changes to clinical management plan based on a review of clinical and radiographic
subject data before and after 18F-DCFPyL PET/CT imaging by a central panel of disease
experts using a structured questionnaire

Clinical Protocol:  PyL-2301 
18F-DCFPyL 
Amendment 2: 06 Nov 2017 
Page 19 
5. PPV of 18F-DCFPyL PET/CT imaging in subjects with corresponding histopathology that
is outside the planned protocol surgical template or biopsy site
6.
INVESTIGATIONAL PLAN
6.1. 
Overall Study Design
This is an open-label, non-randomized, Phase 2/3, multi-center study designed to evaluate the 
safety and diagnostic performance of 18F-DCFPyL PET/CT imaging to determine the presence or 
absence of metastatic prostate cancer in subjects with at least high risk prostate cancer who are 
planned for radical prostatectomy [RP] with pelvic lymph node dissection [PLND]) (cohort A), 
and subjects with radiologic evidence of local recurrence or new or progressive metastatic 
disease (cohort B). 
Eligible subjects (see Section 7.1 for Inclusion Criteria) will be enrolled in a non-randomized, 
sequential manner, with competitive enrollment between study sites.   
Diagnostic performance characteristics of 18F-DCFPyL PET/CT imaging will be evaluated using 
histopathology as the truth standard.  See Section 8.4 for details on blinding.  
The study will explore changes to clinical management plans based on data before and after 18F-
DCFPyL PET/CT imaging.  
This study is planned to be performed in approximately 10 sites in the United States and Canada. 
See Figure 1 and Table 3 for the study schema and schedule of assessments.  
6.2. 
Number of Subjects 
Approximately 377 subjects are planned to be dosed in this study: 
•
Approximately 262 subjects will be dosed in Cohort A.
•
Approximately 115 subjects will be dosed in Cohort B.
See Section 7 for complete eligibility details and Section 12.1 for complete sample size 
assumptions. 
6.3. 
Treatment Assignment 
All subjects will be administered 9 ± 1 mCi (333 ± 37 MBq) 18F-DCFPyL Injection followed by 
PET/CT imaging as illustrated in the schema below.  See Section 9.6 Study Drug Administration 
and Table 3 Schedule of Assessments for complete details.   

Clinical Protocol:  PyL-2301 
18F-DCFPyL 
Amendment 2: 06 Nov 2017 
Page 20 
Figure 1: 
Study Schema 
6.4. 
Dose Adjustment Criteria 
Dosing adjustments of 18F-DCFPyL Injection are not permitted.   
6.5. 
Study Duration 
The duration of subject participation will be from informed consent through 18F-DCFPyL 
PET/CT scanning and follow-up visit, a total maximum duration of 58 days.   
6.6. 
Safety Monitoring 
An independent Data Monitoring Committee (DMC) will not be used for this open label study.  
However, safety monitoring will consist of continuously monitoring adverse events on an 
ongoing basis in accordance with Section 11.  A Safety Review Committee, consisting of 
Sponsor representatives (e.g., Medical Monitor, Clinical Operations designee, Biometrics 
designee) and at least one active Principal Investigator will also review data on an ongoing basis 
to assess subject safety, eligibility and baseline characteristics through listings, tables and subject 
profiles. 
6.7. 
Criteria for Study Termination 
The Sponsor reserves the right to terminate the study at any time. In the event of serious, 
unexpected and related adverse events, the program may be stopped prematurely upon advice 
from the Safety Review Committee, the Sponsor or upon request from the FDA.  In addition, the 
Sponsor or the Institutional Review Board (IRB) or Ethics Committee (EC) may terminate an 
investigational site for the following (but not limited to) reasons:  
•
If any safety issues occur;
•
Failure of the Investigator to comply with pertinent International Conference on
Harmonisation (ICH) E6 guidelines on Good Clinical Practice (GCP) guidelines and
regulations;
•
If serious protocol violations occur;

Clinical Protocol:  PyL-2301 
18F-DCFPyL 
Amendment 2: 06 Nov 2017 
Page 21 
•
Submission of knowingly false information from the research facility to the Sponsor,
Clinical Monitor, or other party involved in the study;
•
Failure of the Investigator to enroll subjects into the study at an acceptable rate as
agreed-upon with the Sponsor
Table 3: Schedule of Assessments 
Screening
/ Baseline 
18F-
DCFPyL 
Dosing 
18F-
DCFPyL 
Imaging 
Pre-
Surgery/Biopsy 
Follow-Up 
Day-30 to 
Day 1 
Day 1 
1-2 Hours
Post
Dosing
Within 28 Days 
Post Dosing 
Cohorts A and B 
Informed Consent & Eligibility 
X 
Demographics (date of birth, race, 
ethnicity, height, weight, BMI) 
X 
Medical History (see Section 11.1.1)  
X 
Prior Cancer Medications & 
Treatments 
X 
Clinical Labs (Hematology, 
Chemistry) see Table 6  
X1 
X 
PSA (Total) & Testosterone 
X1 
Vital Signs (Blood Pressure, Heart 
Rate, Temperature, Respiratory Rate) 
X 
X 
(pre-
dosing) 
X 
(pre-
imaging) 
X 
12-Lead Electrocardiogram (ECG)
(see Section 11.1.4)
X 
(pre-
dosing) 
X 
(pre-
imaging) 
18F-DCFPyL Administration (see 
Section 9) 
X 
Whole Body PET/CT (see 
Section 10.1) 
X 
Adverse Events (see 
Section 11.2.1.1)  
X 
X5 
Concomitant Medications (see 
Section 8.2) 
X 
X 
X 
Conventional Imaging (CT or MRI, 
Bone Scan) (see Section 10.1)  
X2 
Surgery or Image-Guided Biopsy 
X3,6 

Clinical Protocol:  PyL-2301 
18F-DCFPyL 
Amendment 2: 06 Nov 2017 
Page 22 
Table 3: Schedule of Assessments 
Screening
/ Baseline 
18F-
DCFPyL 
Dosing 
18F-
DCFPyL 
Imaging 
Pre-
Surgery/Biopsy 
Follow-Up 
Day-30 to 
Day 1 
Day 1 
1-2 Hours
Post
Dosing
Within 28 Days 
Post Dosing 
Subset of Cohort A or B at Johns Hopkins University only for Pharmacokinetic (PK) 
Analysis 
Blood Collection  
X (9 
collections)4 
Urine Collection 
X (3 
collections)4 
Whole Body PET/CT 
X (3 
scans)4 
1 To be collected prior to dosing, if collected on day of dosing.  If PSA and testosterone have not been tested within 30 
days of study drug injection, a blood draw will be collected prior to dosing. 
2 If not obtained as standard of care ≤ 6 weeks (Cohort A) or ≤ 4 weeks (Cohort B) prior to Day 1. Na-18F-PET bone 
scans conducted at screening must be at least 10 hours prior to dosing (see Section 7.2).   
3 Surgery or biopsy to occur at least 12 hours from time of 18F-DCFPyL dosing but not more than 28 days from 
dosing.  In Cohort B, imaging used to guide biopsy (i.e., CT, MRI) will be submitted to a central core imaging lab.  
4 See Section 10.6  for complete details. Analysis should occur immediately following last sample collected. 
5 A safety phone call will also occur 7(±3) days post-dosing [if surgery (Cohort A) or biopsy (Cohort B) has not yet 
occurred] and 21(±7) days post biopsy (Cohort B).  See Section 11.2.1.1 for complete details. 
6  If a subject’s planned procedure (RP or biopsy) for prostate cancer changes following 18F-DCFPyL imaging, the 
alternate or additional prostate cancer procedure and corresponding histopathology data will be recorded in the 
electronic case report form (eCRF).

Clinical Protocol:  PyL-2301 
18F-DCFPyL 
Amendment 2: 06 Nov 2017 
Page 23 
7.
SELECTION AND WITHDRAWAL OF SUBJECTS
7.1. 
Subject Inclusion Criteria
Subjects must meet all of the following inclusion criteria: 
All Cohorts: 
1. Adults ≥18 years of age.
2. Subjects provide signed informed consent and confirm that they are able and willing to
comply with all protocol requirements.
3. Histologically confirmed adenocarcinoma of the prostate.
Cohort A Only: 
4. At least high risk prostate cancer defined by NCCN Guidelines Version 3.2016 (clinical
stage ≥T3a or PSA >20 ng/mL or Gleason score ≥8).47
5. Scheduled or will be scheduled to undergo radical prostatectomy with PLND.
Cohort B Only: 
6. Radiologic evidence of local recurrence or new or progressive metastatic disease
demonstrated on anatomical imaging (CT, MRI, or ultrasound), whole-body bone scan
(99mTc-MDP or Na18F) within 4 weeks of Day 1.
7. If prior treatment with radiation or ablative therapy, evidence of recurrence outside the
confines of prior treated site(s).
8. Scheduled or will be scheduled for percutaneous biopsy of at least one amenable lesion.
7.2. 
Subject Exclusion Criteria 
Subjects meeting any of the following exclusion criteria are not eligible for this study: 
All Cohorts: 
9. Subjects administered any high energy (>300 KeV) gamma-emitting radioisotope within
five physical half-lives, or any IV iodinated contrast medium within 24 hours, or any high
density oral contrast medium (oral water contrast is acceptable) within 5 days, prior to
study drug injection.
10. Subjects with any medical condition or other circumstances that, in the opinion of the
investigator, compromise obtaining reliable data, achieving study objectives, or
completion.
Cohort A Only: 
11. Patients with prior androgen deprivation therapy or any investigational neoadjuvant agent
or intervention

Clinical Protocol:  PyL-2301 
18F-DCFPyL 
Amendment 2: 06 Nov 2017 
Page 24 
Cohort B Only: 
12. Prior radiation or ablative therapy to intended site of biopsy, if within the prostate bed.
13. Initiation of new systemic therapy for recurrent and/or progressive metastatic disease
since radiographic documentation of recurrence/progression.
7.3. 
Subject Withdrawal Criteria 
A patient may withdraw from the study at any time for any reason without prejudice to his/her 
future medical care by the physician or at the study site.  Likewise, the Investigator and/or 
Sponsor have the right to withdraw patients from the study.  Subjects may be discontinued for 
any of the following reasons: 
•
Significant protocol violation or noncompliance (e.g., initiation of treatments
forbidden per Section 7.2)
•
Adverse event that precludes further study participation
•
Best medical interest of the patient (Investigator decision)
•
Sponsor terminates the study
•
Subject requests to be withdrawn from the study
•
Subject is lost to follow-up
•
Death
Should a subject withdraw, all efforts will be made to complete the required study procedures as 
thoroughly as possible.   
Data will be collected for all withdrawn subjects up until the time of discontinuation.  The reason 
for discontinuation from the study will be recorded in the subject’s eCRF.   
8.
TREATMENT OF SUBJECTS
8.1. 
Description of Study Drug
A single administration of 18F-DCFPyL Injection (PyL) will be administered 1-2 hours prior to 
PET/CT imaging on Day 1. 
Table 4: Investigational Product 
Investigational Product 
Product Name 
18F-DCFPyL INJECTION (PyL) 
Dosage Form 
Sterile solution for intravenous injection 
Unit Dose 
9 ± 1 mCi (333 ± 37 MBq) 
Route of Administration 
Intravenous catheter placed in an antecubital vein or an equivalent 
venous access 
Physical Description 
Colorless, particle-free solution 

Clinical Protocol:  PyL-2301 
18F-DCFPyL 
Amendment 2: 06 Nov 2017 
Page 25 
8.2. 
Concomitant Medications and Procedures 
All concomitant medications and medical procedures that occur within 7 days of consent will be 
recorded.  
Any new prostate cancer therapy is strictly prohibited from time of dosing (Day 1) to surgery 
(Cohort A), or from time of radiographic documentation of disease progression to biopsy (Cohort 
B).  If a subject reports having received a new prostate cancer therapy (e.g., hormone, drug, 
biologic, radiologic, or chemotherapy) or alternate medical procedure(s) for prostate cancer, 
during these time periods, the subject should be discontinued from the study.   
Medical procedure(s) and histopathology data for subjects who do not receive the planned 
protocol procedure but who received alternate or additional medical procedure(s) for prostate 
cancer will be recorded in the eCRF. 
8.3. 
Treatment Compliance 
All 18F-DCFPyL drug injected will be administered under the supervision of the investigator, or 
qualified designee.  Details of the study drug injection will be captured in each subject’s source 
documents. 
8.4. 
Randomization and Blinding 
This is an open-label, non-randomized study.  Three independent readers from a central imaging 
core lab will be given access to 18F-DCFPyL PET/CT imaging, conventional imaging, and 
biopsy-guided imaging.  The central readers will be blinded to all other clinical information and 
radiology assessments.  Likewise, the Investigator is responsible for ensuring that local 
pathologists who generate the histopathology results for the primary endpoint remain blinded to 
all imaging results.   
9.
STUDY DRUG MATERIALS AND MANAGEMENT
9.1. 
Study Drug
Please reference Section 8.1 for a description of the study drug. 
9.2. 
Restrictions 
9.2.1. 
Food and Fluid Intake 
There are no dietary or food restrictions for this trial. 
Increased fluid intake should occur before and after image acquisition to maintain proper 
hydration throughout the study period and decrease radiation exposure to the urinary bladder.  To 
enhance imaging, subjects should be encouraged to void post study drug injection and prior to 
imaging. 
Subjects should follow pre-imaging and preoperative guidelines as per institutional practices and 
in accordance with standard of care principles. 

Clinical Protocol:  PyL-2301 
18F-DCFPyL 
Amendment 2: 06 Nov 2017 
Page 26 
9.2.2. 
Activity 
The radioactivity administered in this study is similar to other diagnostic radiopharmaceuticals 
and should be managed according to institutional policies.   
9.3. 
Study Drug Packaging and Labeling 
The final drug product (18F-DCFPyL) is a clear, colorless injectable solution at a strength of 5-
75 mCi/mL (185-2775 MBq/mL) 18F-DCFPyL at End of Synthesis (EOS).  18F-DCFPyL will be 
dispensed and filled into a unit-dose syringe.  The final drug product will be placed into a lead 
pig and delivered to the clinical site in shipping containers with lead shielding.  
Labels will be generated according to local policies and meet minimum requirements for labeling 
radioactive materials in compliance with federal, state, and local pharmacy regulations.  
Progenics minimum requirements for the syringe label will include the following:  subject 
identifier, product name, dispensing lot number, ordered dose, dispense date/time, dispensed 
activity and volume, and beyond use date (BUD).  An auxiliary sticker reading “New Drug—
Limited by Federal Law to Investigational Use” shall be affixed to the unit-dose container. 
9.4. 
Study Drug Storage 
The study drug should be maintained at room temperature within the received lead shield unit-
dose system until time of administration.   
9.5. 
Study Drug Preparation 
The final drug product is supplied to each institution on the day of administration in a unit-dose 
syringe with no additional preparation required. Institutional policies and standard operating 
procedures (SOPs) should be followed for receipt and appropriate radiation safety handling.  
Before and after each administration, measure the amount of radioactivity in the syringe using an 
appropriate dose calibrator. Apply decay correction if necessary and calculate the administered 
dose accordingly. 
9.6. 
Administration 
Please see the Imaging Manual for complete details including pre-and post-injection 
measurement of the 18F-DCPyL Injection dose syringe.  Administration must occur by the 
labeled expiration time. 
1. Place an intravenous catheter in an antecubital vein or an equivalent venous access.
2. Ensure patency of the line with a saline flush.
3. Inject a bolus of 9±1 mCi (333±37 MBq) of 18F-DCPyL into the IV line or equivalent
venous access by slow push from the appropriately shielded syringe according to normal
local practices.
4. Administer an intravenous flush (e.g., 5-10 ml sterile Sodium Chloride Injection, 0.9%),
to ensure full delivery of the dose.

Clinical Protocol:  PyL-2301 
18F-DCFPyL 
Amendment 2: 06 Nov 2017 
Page 27 
If dose extravasation is noticed during or after completion of the drug administration: 
1. Try to aspirate as much extravasated drug as possible through the still-intact catheter.
2. Imaging should proceed unless contraindicated for safety reasons.
3. Examine the skin area for local toxicity before discharge, and instruct subject to contact
site immediately if local symptoms at injection site do not improve or worsen.
4. Note the event as an Adverse Event in the CRF and notify the Sponsor within 24 hours.
9.7. 
Study Drug Accountability 
In accordance with ICH and FDA requirements, the investigator and/or drug dispenser must at 
all times account for all study drug furnished to the institution and prepared for the patient, 
whether used or unused.   
No study agent is to be used outside of this study.  Accurate and adequate accountability records 
must be maintained by the radiopharmacy, hot lab or nuclear medicine department responsible 
for receipt and dispensation of study drug.  Records should include at minimum: 
•
Dates of receipt, lot number and quantities received from Sponsor or designee;
•
Dates, subject numbers, and amount dispensed for administration to specific subjects;
•
If applicable, dates, lot numbers, and drug quantities destroyed.
The investigator is responsible for ensuring that study agents are administered only to subjects 
included in this study in accordance with the study protocol. 
Throughout the study, drug accountability will be performed by appropriate Sponsor personnel 
and when appropriate, reconciliation will be performed. 
9.8. 
Study Drug Handling and Disposal 
18F-DCFPyL Injection is a radioactive drug and should be handled by personnel trained in the 
proper use and disposal of radiopharmaceuticals according to institutional policies and applicable 
regulations or guidance.  When handling and administering 18F-DCFPyL Injection, follow 
aseptic procedures and use effective radiation shielding, and appropriate safety measures to 
minimize radiation exposure.   
Empty or unused product should be decayed at the site according to institutional policies and 
applicable state and federal regulations.  Record the use and/or decay of study agent on the Drug 
Accountability record.   

Clinical Protocol:  PyL-2301 
18F-DCFPyL 
Amendment 2: 06 Nov 2017 
Page 28 
10.
ASSESSMENT OF EFFICACY
10.1. 
Image Acquisition 
10.1.1. 
18F-DCFPyL PET/CT (all cohorts) 
18F-DCFPyL PET imaging will be performed on local PET/CT scanners with CT for correction 
of physical effects (e.g., attenuation, scatter) and anatomic localization.   
At 1-2 hours post 18F-DCFPyL injection, the subject will be asked to void, and a whole body CT 
and PET scan will be acquired from the mid-thigh through the vertex of the skull.  Parameters for 
PET/CT scanning can be found in the Imaging Manual.   
10.1.2. 
Bone Scan (all cohorts) 
A radionuclide bone scan (either 99mTc-MDP or 18F-NaF PET/CT, depending upon the site’s 
standard of care) will be obtained at Screening if one has not been obtained within six weeks 
(Cohort A) or four weeks (Cohort B) prior to study drug injection.  If conducted as part of 
Screening, 18F-NaF PET bone scans must be done at least five physical half-lives (10 hours) 
prior to 18F-DCFPyL injection.  Bone scan images will be submitted to the independent central 
imaging core lab per instruction in the Imaging Manual for assessment. 
10.1.3. 
CT or MRI (all cohorts) 
A contrast-enhanced CT of the chest, abdomen and pelvis (or non-contrast CT chest with 
Gadolinium-enhanced MRI of the abdomen and pelvis for subjects who have a medical 
contraindication to iodinated contrast) will be obtained at Screening if not already obtained 
within 6 weeks (Cohort A) or 4 weeks (Cohort B) prior to study drug injection.  If CT is 
conducted at Screening, IV iodinated contrast medium cannot be administered within 24 hours of 
study drug injection.  High density oral contrast medium (oral water contrast is acceptable) 
cannot be administered within 5 days prior to study drug injection.  Copies of baseline CT or MR 
images will be submitted to the independent central imaging core lab per instruction in the 
Imaging Manual for assessment. 
10.1.4. 
Biopsy Guided Imaging (cohort B only) 
In Cohort B, imaging used to guide biopsy (i.e., CT/MRI) will be collected and reviewed 
centrally to confirm the biopsy location in the area of interest.  The instruction for capturing 
biopsy images and directions for submitting the images to the independent central imaging core 
lab will be found in the Image Guided Biopsy Manual. 
10.2. 
Image Interpretation 
An independent imaging core lab will receive and evaluate 18F-DCFPyL PET/CT baseline, 
conventional images, and imaging used to guide biopsy (i.e., CT, MRI).  The processes for 
image acquisition, transmittal and interpretation are detailed in the Imaging Manual and Imaging 
Review Charter documents.   

Clinical Protocol:  PyL-2301 
18F-DCFPyL 
Amendment 2: 06 Nov 2017 
Page 29 
10.3. 
Prostatectomy and Lymphadenectomy 
Within 28 days post-study drug injection, all subjects in Cohort A will undergo standard of care 
RP with PLND as detailed in the Surgical Manual.  Extent of PLND will be captured in the 
eCRF. 
Surgical staff will label all specimens removed during surgery to correlate with the specific 
anatomic location of removal, in accordance with the Surgical Manual.   
Should a subject receive alternate or additional procedure(s) for prostate cancer after dosing, the 
procedure and corresponding histopathology data will be recorded in the eCRF.   
10.4. 
Interventional Radiology 
Up to two lesions (one bone and one soft-tissue lesion, wherever feasible) may be biopsied in 
cohort B, within 28 days following 18F-DCFPyL imaging.  If more than one lesion is obtained, 
the interventional radiologist will identify the specimen to be evaluated for diagnostic assessment 
and statistical analysis.  The lesions most preferred for biopsy will be those that are suspicious on 
all or most imaging modalities and are in the investigators judgement safe for biopsy.  The final 
biopsy site will be decided in consultation with the Interventional Radiology service for 
feasibility.  Details regarding the collection of imaging used to guide biopsy (e.g., X-ray, CT, 
MRI) and transmittal to the central imaging lab can be found in the Image Guided Biopsy 
Manual.  Images will be reviewed centrally to confirm uptake of 18F-DCFPyL in the area of 
interest. 
Should a subject receive alternate or additional procedure(s) for prostate cancer after dosing, the 
procedure and corresponding histopathology data will be recorded in the eCRF.  
10.5. 
Biopsy and Surgical Pathology 
Immediately following biopsy or surgery, the specimens will be sent for histopathological 
processing and analysis at the site in accordance with the study Pathology Manual.   
Gross handling of the prostate gland and lymphadenectomy specimens, if applicable, will include 
whole gland assessment and sectioning of the entire prostate gland, overall measurement of 
specimen size, lesion location, dissection and description (including location) of identified lymph 
nodes, and submission of lymph nodes in their entirety plus all remaining fibroadipose tissue for 
each harvested regional packet.  Histopathology results of the prostate gland and pelvic lymph 
nodes (Cohort A) or biopsy location (Cohort B) will be recorded in the eCRF.  
Should a Cohort A subject forego RP surgery and undergo alternative procedure for prostate 
cancer (e.g., biopsy), the procedure and corresponding histopathology data will be recorded in 
the eCRF.  Likewise, should a Cohort B subject receive additional procedure for prostate cancer, 
the procedure and corresponding histopathology data will be recorded in the eCRF.  
10.6. 
Pharmacokinetics 
A total of 10 subjects from either cohort at the JHU site will complete the pharmacokinetics (PK) 
portion of the study.  For detailed instructions on sample collection, processing, and analysis, 
please refer to the PK Manual. 

Clinical Protocol:  PyL-2301 
18F-DCFPyL 
Amendment 2: 06 Nov 2017 
Page 30 
A 4.5 mL blood sample will be collected at the following nine time points:  pre-dose, 5±2 m, 
15±2 m, 30±5 m, 1±0.25 hr, 2±0.25 hr, 4±0.25 hr, 6±0.25 hr, and 8±0.25 hr post-dose.   
Urine samples will be collected over the following intervals: 0-2 hr, 2-4 hr and 4-8 hr post dose. 
Whole body PET/CT scans will be collected at three time points:  up to 17 minutes after PyL 
injection and prior to voiding, 1± 0.25 hr and 4± 0.25 hr post dose. 
Table 5: PK Sampling & Imaging Timepoints 
Procedure 
Pre- 
dose 
0 
hr 
5±2 
m 
15± 
2 m 
30± 
5 m 
1± 
0.25 
hr 
2± 
0.25 
hr 
3± 
0.25 
hr 
4± 
0.25 
hr 
6± 
0.25 
hr 
8± 
0.25 
hr 
18F-DCFPyL 
Administration 
X 
Blood & Plasma 
Collection 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urine 
Collection 
<-----------X-----------> 
<-----X-----> 
<------X------> 
18F-DCFPyL 
PET/CT 
Imaging 
X 
X 
X 
Analysis will be generated as described below and in Section 12.5.4.  Aliquots of blood, plasma 
and urine samples will be batch counted in an automated gamma counter immediately following 
the sample collection period.  Resulting raw radioactivity counts will be converted into 
radioactivity concentrations using an aliquot of the dosing formulation as a reference standard.   
Blood concentration-time data will be computed by non-compartmental analysis and 
pharmacokinetic parameters, e.g., Cmax, AUC, CL, Vss, and MRT will be generated.  Ratios of 
blood to plasma radioactivity at each time point will be calculated. 
The total amount of excreted radioactivity per urine collection interval will be calculated as a 
product of urine radioactivity concentration and volume, and then expressed as a percent of 
administered dose.  
Metabolic profiles in urine will be determined using radio-chromatographic methods.  The areas 
under the radio-chromatographic peaks corresponding to the parent compounds and putative 
metabolites, if applicable, will be used in the qualitative assessment of metabolic profiles in 
urine. 
Whole-body PET/CT images acquired immediately after PyL injection and at 1 hr and 4 hr post-
dose will be used to obtain volumes and activity concentrations for selected tissues/organs.  
Based on these data, time-integrated activity coefficients will be derived and may be used for 
subsequent calculation of radiation absorbed doses using the OLINDA/EXM software.  This 
analysis will be described in a dosimetry report for 18F-DCFPyL. 

Clinical Protocol:  PyL-2301 
18F-DCFPyL 
Amendment 2: 06 Nov 2017 
Page 31 
11.
ASSESSMENT OF SAFETY
11.1. 
Safety Parameters 
11.1.1. 
Demographic/Medical History 
Demographic and baseline information, including date of birth, race, and ethnicity, will be 
collected.   
A complete prostate medical history will be obtained at the first screening visit.  Prostate medical 
history includes review of prostate disease history, prostate cancer staging, PSA results, biopsy 
results, and all past/present therapies.   
Other clinically relevant medical history will be collected prior to study drug administration.  
This should include any past and/or current medical conditions that, in the opinion of the 
investigator, are clinically relevant regardless of whether it has resolved. Special attention should 
be paid to prior malignancies other than prostate cancer or concurrent or past conditions that can 
change pelvic anatomy or cause lymphadenopathies (e.g., viral, bacterial or parasitic infections). 
11.1.2. 
Vital Signs 
Vital sign measurements will include temperature, respiratory rate, blood pressure, and heart 
rate.  All measurements should be obtained from the subject in the sitting position and measured 
at two intervals on the day of dosing, including pre-dosing and pre-imaging. 
11.1.3. 
Weight and Height 
Height, weight, and BMI at screening will be captured. 
11.1.4. 
Electrocardiogram (ECG) 
A 12-lead electrocardiogram (ECG) will be taken at two intervals on the day of dosing, including 
prior to dosing and prior to imaging.  Please refer to the ECG Procedure Manual for acquisition 
and transmittal details.  The onsite Investigator has the responsibility to evaluate the ECG for the 
assessment of subject safety.  Adverse events will be reported in the CRF.   
11.1.5. 
Laboratory Assessments 
11.1.5.1. Hematology, Blood Chemistry, PSA and Testosterone 
A blood draw will be collected at the screening and follow-up visits as stated in Table 6.  
Clinical hematology and blood chemistry will be evaluated for safety monitoring.  If PSA and 
testosterone have not been tested within 30 days of study drug injection, a blood draw will be 
collected prior to dosing. 

Clinical Protocol:  PyL-2301 
18F-DCFPyL 
Amendment 2: 06 Nov 2017 
Page 32 
Table 6: Clinical Laboratory Tests 
Category 
Analytes 
Frequency1 
Hematology 
CBC:  WBC differential (neutrophils, 
lymphocytes, monocytes, eosinophils, basophils), 
WBC count, RBC count, Hematocrit, 
Hemoglobin, Platelets 
Screening, Follow-Up 
Chemistry 
CMP:  Sodium, Potassium, Calcium, Chloride, 
Glucose, BUN, Creatinine, Total Bilirubin,  ALT, 
AST, Alkaline Phosphatase, Albumin, Total 
Protein 
Screening, Follow-Up 
PSA 
Total 
Screening 
Testosterone 
Total 
Screening 
CBC=complete blood count; WBC=white blood cell; RBC=red blood cell; CMP=comprehensive metabolic panel; 
BUN=blood urea nitrogen; ALT=alanine aminotransferase; AST=aspartate aminotransferase; PSA=prostate-specific 
antigen 
1 Blood draws and laboratory testing will be conducted according to local standard practices.  PSA and testosterone 
resulted within 30 days of Day 1 does not need to be re-tested. 
11.2. 
Adverse and Serious Adverse Events 
11.2.1. 
Definition of Adverse Events 
11.2.1.1. Adverse Event (AE) 
An AE is the development of an undesirable medical occurrence or the deterioration of a pre-
existing condition following or during exposure to a pharmaceutical product, whether or not 
considered related to the product.   
All AEs (related and unrelated) will be collected on the day of, after 18F-DCFPyL dosing and at 
time of follow-up visit (pre-surgery/biopsy).  Adverse events will also be assessed via a safety 
phone call at the following timepoints, if applicable:  1) 7 (±3) days post study drug injection (if 
surgery or biopsy has not yet occurred), and 2) 21 (±7) days post biopsy.   
All AEs, whether or not they are related to study drug, must be recorded on the study case report 
forms.  
11.2.1.2. Serious Adverse Event (SAE) 
A serious adverse event is an AE that fulfils one or more of the following: 
•
Results in death
•
It is immediately life-threatening
•
It requires in-patient hospitalization or prolongation of existing hospitalization
•
It results in persistent or significant disability or incapacity

Clinical Protocol:  PyL-2301 
18F-DCFPyL 
Amendment 2: 06 Nov 2017 
Page 33 
•
Results in a congenital abnormality or birth defect of a subject’s child
•
It is an important medical event that may jeopardize the patient or may require
medical intervention to prevent one of the outcomes listed above.
All SAEs that occur after any patient/subject has been dosed until study completion, whether or 
not related to the study, must be recorded on forms provided by the Sponsor, or designee. 
11.3. 
Relationship to Study Drug 
The Principal Investigator or Sub-Investigator must make the determination of relationship to the 
investigational product for each AE (Unrelated or Related).  The Investigator should decide 
whether, in his or her medical judgment, there is a reasonable possibility that the event may have 
been caused by the investigational product.  If no valid reason exists for suggesting a 
relationship, then the AE should be classified as “unrelated.”  If there is any valid reason, even if 
undetermined, for suspecting a possible cause-and-effect relationship between the investigational 
product and the occurrence of the AE, then the AE should be considered “related.” 
11.4. 
Recording Adverse Events 
Adverse events spontaneously reported by the patient/subject and/or in response to an open 
question from the study personnel or revealed by observation will be recorded during the study at 
the investigational site.   
The investigator should assess all clinical laboratory results for clinical significance and record 
the assessment in source documents.  The investigator should evaluate any laboratory result 
change from pre- and post-study drug administration to determine if the change meets the 
definition of an AE or SAE.  Record any clinically significant lab results determined to meet the 
definition of an AE and SAE on the AE eCRF and SAE Report Form, respectively. 
Information about AEs and SAEs will be collected from the first administration of study drug 
until the pre-surgery/biopsy follow-up visit.  The AE term should be reported in standard 
medical terminology and be the medical diagnosis when possible.  For each AE, the investigator 
will evaluate and report the onset (date and time), resolution (date and time), intensity, causality, 
action taken, serious outcome (if applicable), and whether or not it caused the patient to 
discontinue the study. 
Intensity will be assessed according to the NCI CTCAE, version 4.03.  If the CTCAE grading is 
not defined in the NCI CTCAE grading table for a particular AE, severity will be rated according 
to the following definitions 
•
Mild (awareness of sign or symptom, but easily tolerated)
•
Moderate (discomfort sufficient to cause interference with normal activities)
•
Severe (incapacitating, with inability to perform normal activities)
•
Life Threatening (immediate risk of death from the event as it occurred)
•
Death (death related to adverse event)

Clinical Protocol:  PyL-2301 
18F-DCFPyL 
Amendment 2: 06 Nov 2017 
Page 34 
It is important to distinguish between serious and severe AEs.  Severity is a measure of intensity 
whereas seriousness is defined by the criteria under Section 11.2.1.2.  An AE of severe intensity 
may not be considered serious. 
Should a pregnancy occur, it must be reported and recorded on the Sponsor’s pregnancy form.  
Pregnancy in itself is not regarded as an AE. 
The outcome of all pregnancies (spontaneous miscarriage, elective termination, normal birth or 
congenital abnormality) must be followed up and documented even if the patient was 
discontinued from the study. 
All reports of congenital abnormalities/birth defects are SAEs.  Spontaneous miscarriages should 
also be reported and handled as SAEs.  Elective abortions without complications should not be 
handled as AEs. 
11.5. 
Reporting Serious Adverse Events 
All SAEs (related and unrelated) will be recorded at the same interval defined for AE collection 
as indicated in Section 11.2.1.1 .  Any SAEs considered possibly or probably related to the 
investigational product and discovered by the Investigator at any time after the study should be 
reported.  All SAEs must be reported to Progenics or designee within 24 hours of the first 
awareness of the event.  The Investigator must complete, sign and date the SAE pages, verify the 
accuracy of the information recorded on the SAE pages with the corresponding source 
documents, and send a copy by email or fax to Sponsor, or designee.   
Additional follow-up information, if required or available, should promptly be emailed or faxed 
to Sponsor, or designee via a follow-up SAE form and placed with the original SAE information 
and kept with the appropriate section of the CRF and/or study file. 
Progenics Pharmaceuticals, Inc. is responsible for notifying the relevant regulatory authorities of 
certain events.  It is the Principal Investigator’s responsibility to notify the IRB or IEC of all 
SAEs that occur at his or her site.  Investigators will also be notified of all unexpected, serious, 
drug-related events (7/15 Day Safety Reports) that occur during the clinical trial.  Each site is 
responsible for notifying its IRB or IEC of these additional SAEs. 
12.
STATISTICS
12.1. 
Sample Size 
Approximately 262 subjects will be dosed in cohort A.   No formal power calculations will be 
performed for cohort B; reliable estimates should be achievable from approximately 115 dosed.  
This results in a total sample size of approximately 377 subjects dosed in the study.   
The primary analysis in Cohort A will test the co-primary endpoints of sensitivity and specificity 
of 18F-DCFPyL PET imaging relative to histopathology for metastatic disease in pre-
prostatectomy patients.  For each co-primary endpoint there will be three independent imaging 
readers.  At least two of the three readers must reject the null hypothesis for specificity to be 
deemed a success.  If specificity is a success, then the same two readers need to reject the null 

Clinical Protocol:  PyL-2301 
18F-DCFPyL 
Amendment 2: 06 Nov 2017 
Page 35 
hypothesis for sensitivity to reach overall success of the primary endpoint.  The null hypotheses 
will be tested in the following order: 
1. Specificity of 18F-DCFPyL PET/CT imaging relative to histopathology in cohort A
H0: πSp = 0.80 versus H1: πSp ≠ 0.80,
2. Sensitivity of 18F-DCFPyL PET/CT imaging relative to histopathology in cohort A
H0: πSe = 0.40 versus H1: πSe ≠ 0.40
where πSe is the true sensitivity and πSp is the true specificity of 18F-DCFPyL PET imaging. 
A total of approximately 262 subjects from Cohort A will provide 80% power to reject the null 
hypothesis about sensitivity at the 5% significance level if the true sensitivity is at least 60% and 
at least 80% power to reject the null hypothesis about specificity at the 5% significance level if 
the true specificity is at least 87.8%.  These calculations are based on the following assumptions:    
•
the probability of a positive histopathology sample in Cohort A is 20%,
The sample size is based on the normal approximation to the binomial distribution without a 
continuity correction48:  
𝑛≥൝
𝑧𝛼/2ඥ𝑃0(1 −𝑃0) + 𝑧𝛽ඥ𝑃1(1 −𝑃1)
𝑃1 −𝑃0
ൡ
2
P0 are P1 are values of sensitivity under the null and alternative hypotheses, respectively.  
After adjusting sensitivity and specificity separately by their corresponding prevalence values, a 
total in 236 evaluable subjects are needed in cohort A.  Assuming 10% drop out or non-evaluable 
rate increases the required number of subjects in cohort A to approximately 262.  
The type I error rate of 5% will be preserved by requiring that both null hypotheses be rejected in 
order to draw the conclusion that 18F-DCFPyL is efficacious for imaging. The second primary 
endpoint is only tested if the first primary endpoint is rejected at 5% per a fixed sequential 
method.  If the first hypothesis fails to be rejected, no further testing will be conducted.  
12.2. 
Analysis Populations 
12.2.1. 
Screened Subjects 
All subjects who sign an informed consent document will be included in the screened subject 
population. 
12.2.2. 
Safety Set 
All subjects who receive any amount of 18F-DCFPyL will be included in the safety set. 
12.2.3. 
Evaluable Set 
Evaluable subjects in Cohort A are those who provide a 18F-DCFPyL PET image result (positive 
or negative) and a corresponding RP histopathology result (positive or negative).   
Evaluable subjects in Cohort B are those who provide a 18F-DCFPyL PET image result (positive 
or negative) and a corresponding biopsy histopathology result (positive or negative for each 

Clinical Protocol:  PyL-2301 
18F-DCFPyL 
Amendment 2: 06 Nov 2017 
Page 36 
subject), along with a conventional image that confirms the location of the histopathology 
sample. 
12.2.4. 
Per Protocol Set 
The per protocol set is the evaluable set, excluding subjects with major protocol deviations 
impacting efficacy endpoint(s). 
12.2.5. 
PK Evaluable Set 
Subjects who provide at least six of the nine scheduled blood samples will be evaluable for PK 
analysis of blood samples.  Subjects with at least two of the three scheduled urines will be 
evaluable for PK analysis of urine samples. 
12.3. 
Endpoints and Derivations 
12.3.1. 
Sensitivity, Specificity, PPV, and NPV 
Table 7 will be used to classify the combined pelvic lymph node packets (left or right) from 
Cohort A and biopsy from Cohort B according to its 18F-DCFPyL image result (positive or 
negative) generated from central imaging review and its histopathology result (positive or 
negative for prostate cancer) generated by the sites’ pathology review.    Nodes identified on 18F-
DCFPyL PET/CT images in areas that were not removed in surgery for Cohort A will not be 
tabulated due to absence of histopathology. 
Table 7: Classification of 18F-DCFPyL Imaging Result and Histopathology Result for 
Cohorts A and B Separately 
Histopathology Result 
18F-DCFPyL Image 
Positive* 
Negative 
Positive 
TP 
FP 
I(p) 
Negative 
FN 
TN 
I(n) 
R(p) 
R(n) 
N1 
TP=true positive; FP=false positive; FN=false negative; TN=true negative.   
R(p) and R(n) denote the subjects with a positive or negative lobe or biopsy, respectively, based on histopathology. 
I(p) and I(n) denote the subjects with a positive and negative lesion, respectively, based on the 18F-DCFPyL image. 
N1 indicates the number of subjects with evaluable pelvic lymph node packets from Cohort A or the number of 
subjects with evaluable biopsies from Cohort B. 
*Positive histopathology should be for prostate cancer only.
The following statistics will be computed: 
•
Sensitivity = TP/R(p),
•
Specificity = TN/R(n),
•
Positive predictive value (PPV) = TP/I(p),
•
Negative predictive value (NPV) = TN/I(n).

Clinical Protocol:  PyL-2301 
18F-DCFPyL 
Amendment 2: 06 Nov 2017 
Page 37 
For Cohort A, a true positive or true negative must be determined from imaging and 
histopathology aligning on outcome overall. 
12.3.2. 
Lesions Per Subject 
The number of lesions detected on the 18F-DCFPyL PET/CT image in each of bone, lymph 
nodes, soft tissue, and prostate gland will be determined by each of the three central imaging 
core lab independent readers.  The number of lesions per subject per region will be computed for 
each subject based on each reader’s lesion count. 
12.3.3. 
Change from Baseline 
For laboratory data, baseline will be the screening/baseline value.  Change from baseline will be 
computed as the pre-surgery/biopsy follow-up value minus the baseline value +1. 
For ECG data, baseline will be the pre-dose value.  Change from baseline will be computed as 
the post-dose value minus the pre-dose value +1. 
For vital signs, baseline will be the pre-dose value.  Change from baseline will be computed as 
the post-dose value minus the pre-dose value +1 and the pre-surgery/biopsy value minus the 
baseline value +1. 
12.3.4. 
Pre-Treatment and Concomitant Medications 
Pre-treatment medications are those administered prior to 18F-DCFPyL administration; 
concomitant medications are those administered from 18F-DCFPyL administration through last 
study visit.   
12.3.5. 
Treatment-Emergent Adverse Events 
Treatment-emergent adverse events will be those observed from the day of 18F-DCFPyL 
administration until 7 (±3) days post study drug injection [if surgery (Cohort A) or biopsy 
(Cohort B) has not yet occurred] and 21 (±7) days post biopsy in Cohort B.   
12.4. 
Missing Data 
No imputation of missing data will be applied. 
12.5. 
Analyses 
In general, continuous endpoints will be summarized by visit using summary statistics: sample 
size, mean, standard deviation, median, minimum, and maximum.  Categorical endpoints will be 
summarized by visit using frequencies and percentages. 
12.5.1. 
Subject Characteristics 
A disposition table will be presented to show how many subjects were screened, the number and 
percentage of subjects in each population set, study completers, and early discontinuations along 
with reasons for discontinuation.  
Baseline characteristics (age in years, categorical age [<65 years, ≥65 years], race, gender, 
ethnicity, height [cm], weight [kg], BMI [kg/m2]) will be summarized for all analysis population 

Clinical Protocol:  PyL-2301 
18F-DCFPyL 
Amendment 2: 06 Nov 2017 
Page 38 
sets.  Medical history verbatim terms will be coded using Medical Dictionary for Regulatory 
Activities (MedDRA).  Subject frequencies and percentages will be tabulated by system organ 
class (SOC) and preferred term (PT) for all analysis population sets.  Prior prostate cancer 
medical history will be summarized for all analysis populations.  Type of CT, MRI or bone scans 
will be summarized along with days each occurred prior to study drug administration by all 
analysis populations. 
Medications will be coded using the WHO Drug Dictionary.   Pre-treatment medications will 
each be summarized by ATC4 class and generic name for all analysis population sets.   
12.5.2. 
Efficacy Analysis 
12.5.2.1. Primary Endpoint 
Cohort A 
The primary analysis in Cohort A will be addressed by computing point estimates and 95% two-
sided confidence intervals (CIs) for specificity first and if the null hypothesis is rejected for 
specificity then sensitivity will be tested next.  Both outcomes are on the subject level (one 
overall outcome per subject) in the evaluable set.  If the per protocol population exists then this 
analysis will be performed on the per protocol population as a supplemental analysis.   The 
normal approximation to the binomial distribution will be used.  Sensitivity and specificity will 
be computed for each of three central imaging core lab independent readers. 
The null hypothesis for specificity will be rejected if the lower limit of the 95% CI exceeds 0.80 
for at least two readers.  If statistical significance is achieved for specificity where the null 
hypothesis is rejected, then sensitivity will be tested where the null hypothesis will be rejected if 
the lower limit of 95% CI exceeds 0.40 for the same two readers who rejected the null hypothesis 
for specificity.  
A sensitivity analysis will be performed to allow any 2 of the 3 central readers to reject the null 
hypothesis for sensitivity only after specificity has been deemed a success. This analysis will not 
require the same 2 central readers to reject the null hypothesis for specificity and sensitivity. This 
analysis will be performed for the evaluable and per protocol populations. 
12.5.2.2. Secondary Endpoints 
The following secondary efficacy endpoint analyses will be generated on the evaluable set.  
Point estimates and two-sided 95% CIs will be presented for the following secondary endpoints:   
•
PPV and NPV will be computed for the pelvic lymph node packets (one observation
per subject for cohort A).
•
Sensitivity of 18F-DCFPyL PET/CT imaging within sites of metastasis or local
recurrence relative to histopathology (cohort B)
•
PPV will be computed for the biopsies (one observation per subject for cohort B).
The normal approximation to the binomial distribution will be used for endpoints having one 
observation per subject.  The null hypothesis will be rejected for each if the lower limit of the 

Clinical Protocol:  PyL-2301 
18F-DCFPyL 
Amendment 2: 06 Nov 2017 
Page 39 
95% CI exceeds 0.50 for at least 2 of the 3 central readers. Statistics will be computed for each 
of the three central imaging core lab independent readers. 
Lesions per subject, as detected by 18F-DCFPyL PET/CT and conventional images will be 
summarized for each tissue type (bone, lymph nodes, soft tissue, and prostate gland) and each of 
the three central imaging core lab independent readers using evaluable subjects from both 
cohorts.   
12.5.2.3. Exploratory Analyses 
Analyses will be generated on the evaluable set for the following exploratory endpoints: 
•
The number of lesions per subject will be plotted against baseline PSA and baseline
testosterone for each of the three central imaging core lab independent readers using
evaluable subjects from both cohorts.
•
SUVmax, SUVpeak and SUVr will be summarized for each tissue type (e.g., bone, lymph
nodes, soft tissue, and prostate gland) and each of the three central imaging core lab
independent readers using evaluable subjects from both cohorts.  The relationship
between SUVr in prostatic lesions and baseline PSA and testosterone levels, and Gleason
score at time of radical prostatectomy will be evaluated.
•
Sensitivity, SUVmax, SUVpeak, and SUVr will be computed for the following subgroups in
Cohort A:
-
Previous radiation therapy (yes/no)
-
Previous hormonal therapy (yes/no)
-
Previous chemotherapy (yes/no)
•
SUVmax, SUVpeak, and SUVr will be summarized with positive and negative
histopathology.  Each will be summarized by Gleason score for the single or dominant
prostate tumor nodule.
•
The clinical management plans before and after review of 18F-DCFPyL PET/CT scans
will be summarized.
An exploratory analysis of PPV of 18F-DCFPyL PET/CT imaging in subjects who are excluded 
from the evaluable set but have corresponding histopathology outside the planned protocol 
procedure will be performed on the safety set. 
12.5.3. 
Safety 
All safety parameters will be presented for the safety set. 
12.5.3.1. Exposure 
Volume administered (mL) and activity administered (mCi) will be summarized using the Safety 
Set and the Evaluable Set. 

Clinical Protocol:  PyL-2301 
18F-DCFPyL 
Amendment 2: 06 Nov 2017 
Page 40 
12.5.3.2. Adverse Events 
Adverse event verbatim terms will be coded using MedDRA.  The frequency and percentage of 
subjects with an adverse event and the number of events will be summarized by SOC and PT.  
Adverse events will also be summarized by severity and, separately, by relationship to treatment.  
Serious adverse events, adverse events leading to study discontinuation and adverse events 
leading to death will be listed. 
12.5.3.3. Clinical Laboratory 
Observed values and changes will be tabulated using summary statistics in the safety set. 
12.5.3.4. ECG 
Observed values and changes will be tabulated for each visit using summary statistics.  Shift 
tables comparing pre- to post-dosing categorical ECG values will be presented using the safety 
set. 
12.5.3.5. Vital Signs 
Observed values and changes will be tabulated using summary statistics in the safety set. 
12.5.4. 
Pharmacokinetics 
Mean (±SD) and individual activity-time plots will be presented for blood (mCi/mL), urine (% 
injected dose excreted per collection interval) and selected organs/tissues, including “whole 
body” (% injected dose at each scanning time-point).  Summary statistics (sample size [N], 
arithmetic mean, geometric mean, median, SD, minimum, and maximum) will be presented by 
timepoint for each of blood, urine and selected organs/tissues, including “whole body”.   
Summary statistics will be presented for Cmax, area under the curve (AUC), total clearance (CL), 
steady-state volume of distribution (Vss), and mean residence time (MRT) for the subset of 
subjects (PK evaluable set). 
13.
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS
Data collected during this study may be used to support the development, registration or 
marketing of 18F-DCFPyL.  All data collected during the study will be controlled by Progenics or 
designee and Progenics will abide by all relevant data protection laws.   
The investigator will grant monitor(s) and auditor(s) from Progenics or its designee and 
regulatory authority(ies) access to the subject’s original medical records for verification of data 
entered into the eCRF and to audit the data collection process.  The subject’s confidentiality will 
be maintained and will not be made publicly available to the extent permitted by the applicable 
laws and regulations. 
13.1. 
Study Monitoring 
Before an investigational site can enter a patient into the study, a representative of Sponsor will 
visit the investigational study site to: 

Clinical Protocol:  PyL-2301 
18F-DCFPyL 
Amendment 2: 06 Nov 2017 
Page 41 
•
Determine the adequacy of the facilities
•
Discuss with the investigator(s) and other personnel their responsibilities with regard
to protocol adherence, and the responsibilities of Progenics or its representatives.
This will be documented in a Clinical Study Agreement between Progenics, or
designee and the investigator.
During the study, a monitor from Progenics or designee will have regular contacts with the 
investigational site, for the following: 
•
Provide information and support to the investigator(s)
•
Confirm that facilities remain acceptable
•
Confirm that the investigational team is adhering to the protocol, that data are being
accurately recorded in the case report forms, and that investigational product
accountability checks are being performed
•
Perform source data verification.  This includes a comparison of the data in the case
report forms with the patient’s medical records at the hospital or practice, and other
records relevant to the study.  This will require direct access to all original records for
each patient (e.g., clinic charts).
•
Record and report any protocol deviations not previously sent to the Sponsor, or
designee.
•
Confirm AEs and SAEs have been properly documented on CRFs and confirm any
SAEs have been forwarded to the Sponsor, or designee, and those SAEs that met
criteria for reporting have been forwarded to the IRB.
•
Confirm serious/unexpected/related SAE notification letter(s) from the Sponsor have
been acknowledged and returned to the Sponsor.
The monitor will be available between visits if the investigator(s) or other staff needs 
information or advice. 
13.2. 
Audits and Inspections 
Authorized representatives of the Sponsor, a regulatory authority, an Independent Ethics 
Committee or an Institutional Review Board may visit the site to perform audits or inspections, 
including source data verification.  The purpose of a Sponsor audit or inspection is to 
systematically and independently examine all study-related activities and documents to 
determine whether these activities were conducted, and data were recorded, analyzed, and 
accurately reported according to the protocol, Good Clinical Practice guidelines of the 
International Conference on Harmonization, and any applicable regulatory requirements.   
The investigator should contact Progenics immediately if contacted by a regulatory agency about 
an inspection, and will provide Progenics with the results of any such audits and with copies of 
any regulatory documents related to such audits. 

Clinical Protocol:  PyL-2301 
18F-DCFPyL 
Amendment 2: 06 Nov 2017 
Page 42 
14.
ETHICS
This clinical trial will be conducted in accordance with the ethical principles that have their 
origin in the Declaration of Helsinki and that are consistent with GCP and applicable regulatory 
requirement(s).  The rights, safety, and well-being of the trial subjects are the most important 
considerations and should prevail over interests of science and society. 
14.1. 
Good Clinical Practice (GCP), Laws and Regulations 
The investigator must ensure that he/she and all authorized personnel for the study are familiar 
with the principles of Good Clinical Practice (GCP) and that the study is conducted in full 
conformity with the current revision of the Declaration of Helsinki, ICH Guidelines and 
applicable local laws and regulations, with the understanding that local laws and regulations take 
precedence over respective sections in the Declaration of Helsinki and/or the ICH Guidelines. 
14.2. 
Institutional Review Board (IRB) or Independent Ethics Committee 
(IEC) Approval 
The final study protocol, including the final version of the Informed Consent Form, must be 
approved or given a favorable opinion in writing by an IRB or IEC as appropriate.  The 
investigator must submit documented approval to the Sponsor before he or she can enroll any 
patient/subject into the study. 
The Principal Investigator is responsible for informing the IRB or IEC of any amendment to the 
protocol in accordance with local requirements.  In addition, the IRB or IEC must approve all 
advertising used to recruit patients for the study.  The protocol must be re-approved by the IRB 
or IEC upon receipt of amendments and annually, as local regulations require. 
The Principal Investigator is also responsible for providing the IRB with reports of any 
reportable serious adverse drug reactions from any other study conducted with the investigational 
product.  The Sponsor, or designee, will provide this information to the Principal Investigator. 
Progress reports and notifications of serious adverse drug reactions will be provided to the IRB 
or IEC according to local regulations and guidelines. 
14.3. 
Written Informed Consent 
The Principal Investigator(s) at each center will ensure that the patient is given full and adequate 
oral and written information about the nature, purpose, possible risk and benefit of the study.  
Patients must also be notified that they are free to discontinue from the study at any time.  The 
patient should be given the opportunity to ask questions and allowed time to consider the 
information provided. 
The patient’s signed and dated informed consent must be obtained before conducting any study 
procedures. 
The Principal Investigator(s) must maintain the original, signed Informed Consent Form.  A copy 
of the signed Informed Consent Form must be given to the patient. 

Clinical Protocol:  PyL-2301 
18F-DCFPyL 
Amendment 2: 06 Nov 2017 
Page 43 
14.4. 
Subject Confidentiality 
The Investigator must ensure that the subject’s privacy is maintained.  A subject should only be 
identified by their date of birth and subject number on the case report forms or other documents 
submitted to the Sponsor.  Documents that are not submitted to the Sponsor (e.g., signed 
informed consent form) should be kept in a strictly confidential section of the study file by the 
Investigator. 
Written authorization is to be obtained from each subject prior to enrollment into the study in 
accordance with the applicable privacy requirements [e.g., the Health Insurance Portability and 
Accountability Act of 1996 Standards for Privacy of Individually Identifiable Health Information 
(“HIPAA”) and any other state and country privacy requirements]. 
14.5. 
Financial Disclosure 
All investigators must provide financial disclosure information in accordance with the US Code 
of Federal Regulations Title 21 CFR 54.2 through 54.6. 
15.
DATA HANDLING AND RECORDKEEPING
15.1. 
Case Report Forms and Study Records 
Progenics or designee will provide an electronic case report form (eCRF) and eCRF Completion 
Guidelines for the entry of study data.  eCRFs must be completed for each subject.  All study 
data must be reported accurately on eCRFs from original source data.  Source documents are 
original documents, data and records (e.g., hospital records, office charts, laboratory notes, 
memoranda, evaluation checklists, pharmacy dispensing records, recorded data from automated 
instruments, magnetic media, diagnostic images, subject files).  The investigator will make 
available the source documents for inspection.  This information will be considered as 
confidential. 
The use of eCRFs will encompass electronic data entry, query management and investigator 
approval.  Systems used for electronic data capture will be compliant with FDA regulations 21 
CFR Part 11 and within the constraints of the applicable local regulatory agency guidelines.  
The Investigator or designee will review, sign and date the completed eCRF sections.  This 
signature will indicate a thorough inspection of the data in the eCRF and will certify its content. 
15.2. 
Inspection of Records 
The Sponsor, or designee, will be allowed to conduct site visits to the investigation facilities for 
the purpose of monitoring any aspect of the study.  The Investigator agrees to allow the monitor 
to inspect the drug storage area, study drug stocks, drug accountability records, subject charts 
and study source documents, and other records relative to study conduct.  See Section 13.2. 
15.3. 
Retention of Records 
The Principal Investigator must maintain all documentation relating to the study for a period of 2 
years after the last marketing application approval, or if not approved 2 years following the 

Clinical Protocol:  PyL-2301 
18F-DCFPyL 
Amendment 2: 06 Nov 2017 
Page 44 
discontinuance of the test article for investigation.  If it becomes necessary for the Sponsor or the 
Regulatory Authority to review any documentation relating to the study, the Investigator must 
permit access to such records.  No study document should be destroyed without prior written 
agreement between Sponsor and the investigator. 
16.
PUBLICATION AND DISCLOSURE POLICY
All unpublished documentation [including the protocol, eCRF and Investigator Brochure (IB)] 
given to the investigator is strictly confidential.  All recipients must agree not to disclose the 
information herein contained to any person without the prior written authorization of Progenics.  
The submission of these documents to the IRB is expressly permitted.   
The investigator agrees that Progenics maintains the right to use the results of this study in their 
original form and/or in a global report for submission to governmental and regulatory authorities 
of any country. 
The results of the study may be presented during scientific symposia or published in a scientific 
journal only after review by Progenics in accordance with the guidelines set forth in the 
applicable publication or financial agreement. 

Clinical Protocol:  PyL-2301 
18F-DCFPyL 
Amendment 2: 06 Nov 2017 
Page 45 
17.
REFERENCES
1. Siegel R, Miller KD, Jemal A. Cancer statistics. CA Cancer J Clin. 2017;67:7-30.
2. Shinohara K, Wheeler TM, Scardino PT. The appearance of prostate cancer on transrectal
ultrasonography: correlation of imaging and pathological examinations. J Urol.
1989;142:76–82.
3. Hricak H, Dooms GC, Jeffrey RB, et al. Prostatic carcinoma: staging by clinical
assessment, CT, and MR imaging. Radiology. 1987;162:331–336.
4. Scheidler J, Hricak H, Vigneron DB, et al. Prostate cancer: localization with three-
dimensional proton MR spectroscopic imaging—clinicopathologic study. Radiology.
1999;213:473–480.
5. Blomqvist L, Carlsson S, Gjertsson P, et al. Limited evidence for the use of imaging to
detect prostate cancer: a systematic review. Eur J Radiol. 2014;83:1601–1606.
6. Turlakow A, Yeung HW, Pui J, et al. Fludeoxyglucose positron emission tomography in
the diagnosis of giant cell arteritis. Arch Intern Med. 2001;161:1003–1007.
7. Hofer C, Laubenbacher C, Block T. Fluorine-18-fluorodeoxyglucose positron emission
tomography is useless for the detection of local recurrence after radical prostatectomy.
Eur Urol. 1999;36:31–35.
8. Nunez R, Macapinlac HA, Yeung HW, et al. Combined 18F-FDG and 11C-methionine
PET scans in patients with newly progressive metastatic prostate cancer. J Nucl Med.
2002;43:46–55.
9. Shreve PD, Grossman HB, Gross MD, Wahl RL. Metastatic prostate cancer: initial
findings of PET with 2-deoxy-2-[F-18]fluoro-D-glucose. Radiology. 1996;199:751–756.
10. Ramírez de Molina A, Rodriguez-Gonzalez A, Gutierrez R, et al. Overexpression of
choline kinase is a frequent feature in human tumor-derived cell lines and in lung,
prostate, and colorectal human cancers. Biochem Biophys Res Commun. 2002;296:580–
583.
11. Krause BJ, Souvatzpglou M, Tuncel M, et al. The detection rate of [11C]choline-
PET/CT depends on the serum PSA-value in patients with biochemical recurrence of
prostate cancer. Eur J Nucl Med Mol Imaging. 2008;35:18–23.
12. Rinnab L, Mottaghy FM, Blumstein NM, et al. Evaluation of [11C]choline positron
emission tomography in patients with increasing prostate-specific antigen levels after
primary treatment for prostate cancer. BJU Int. 2007;100: 786–793.
13. Giovacchini G, Picchio M, Coradesschi E, et al. 11C-choline uptake with PET/CT for the
initial diagnosis of prostate cancer: relation to PSA levels, tumor stage and anti-
androgenic therapy. Eur J Nucl Med Mol Imaging. 2008;35:1065–1073.
14. Castellucci P, Fuccio C, Nanni C, et al. Influence of trigger PSA and PSA kinetics on
11C-choline PET/CT detection rate in patients with biochemical relapse after radical
prostatectomy. J Nucl Med. 2009;50:1394–1400.

Clinical Protocol:  PyL-2301 
18F-DCFPyL 
Amendment 2: 06 Nov 2017 
Page 46 
15. Hricak H, Choyke PL, Eberhardt SC, et al. Imaging prostate cancer: a multidisciplinary
perspective. Radiology. 2007;243:28–53.
16. Lawrentschuk N, Davis ID, Bolton DM, Scott AM. Positron emission tomography and
molecular imaging of the prostate: an update. BJU Int. 2006;97:923–931.
17. de Jong IJ, Pruim J, Elsinga PH, et al. 11C-choline positron emission tomography for the
evaluation after treatment of localized prostate cancer. Eur Urol. 2003;44:32–38.
18. Picchio M, Messa C, Landoni C, et al. Value of [11C]choline-positron emission
tomography for re-staging prostate cancer: a comparison with [18F]fluorodeoxyglucose-
positron emission tomography. J Urol. 2003;169:1337–1340.
19. Scattoni V, Picchio M, Suardi N, et al. Detection of lymph-node metastases with
integrated [11C]choline PET/CT in patients with PSA failure after radical retropubic
prostatectomy: results confirmed by open pelvic-retroperitoneal lymphadenectomy. Eur
Urol. 2007;52:423–429.
20. Greco C, Cascini GL, Tamburrini O. Is there a role for positron emission tomography
imaging in the early evaluation of prostate cancer relapse? Prostate Cancer Prostatic Dis.
2008;11:121–128.
21. Chang SS. Overview of prostate-specific membrane antigen. Rev Urol. 2004;6(Suppl
10):S13–S18.
22. Wright GL, Jr, Grob BM, Haley C, et al. Upregulation of prostate-specific membrane
antigen after androgen-deprivation therapy. Urology. 1996;48:326–334.
23. Silver DA, Pellicer I, Fair WR, Heston WD, Cordon-Cardo C. Prostate-specific
membrane antigen expression in normal and malignant human tissues. Clin Cancer Res.
1997;3:81–85.
24. Wong MC, Goggins WB, Wang HH, Fung FD, Leung C, Wong SY, Ng CF, Sung JJ.
Global Incidence and Mortality for Prostate Cancer: Analysis of Temporal Patterns and
Trends in 36 Countries. Eur Urol. 2016 70(5):862-874
25. Dy GW, Gore JL, Forouzanfar MH, Naghavi M, Fitzmaurice C. Global Burden of
Urologic Cancers, 1990-2013. Eur Urol. 2017 71(3):437-446..
26. Racioppi M, Palermo G, D’Addessi A, Pinto F, Sacco E, D’Agostino D, Vittori M, Bassi
PF. Hot topics in urological health economics. A mini review. Archivio Italiano di
Urologia e Andrologia 2012; 84, 2.
27. Hövels AM, Heesakkers RA, Adang EM, Jager GJ, Strum S, Hoogeveen YL, Severens
JL, Barentsz JO. The diagnostic accuracy of CT and MRI in the staging of pelvic lymph
nodes in patients with prostate cancer: a meta-analysis. Clinical radiology. 2008 Apr
30;63(4):387-95.
28. Hillier SM, Maresca KP, Femia FJ, Marquis JC, Foss CA, Nguyen N, Zimmerman CN,
Barrett JA, Eckelman WC, Pomper MG, Joyal JL. Preclinical evaluation of novel
glutamate-urea-lysine analogues that target prostate-specific membrane antigen as
molecular imaging pharmaceuticals for prostate cancer. Cancer research. 2009 Sep
1;69(17):6932-40.

Clinical Protocol:  PyL-2301 
18F-DCFPyL 
Amendment 2: 06 Nov 2017 
Page 47 
29. Pinto JT, Suffoletto BP, Berzin TM, Qiao CH, Lin S, Tong WP, May F, Mukherjee B,
Heston WD. Prostate-specific membrane antigen: a novel folate hydrolase in human
prostatic carcinoma cells. Clinical Cancer Research. 1996 Sep 1;2(9):1445-51.
30. Smith-Jones PM, Vallabahajosula S, Goldsmith SJ, Navarro V, Hunter CJ, Bastidas D,
Bander NH. In vitro characterization of radiolabeled monoclonal antibodies specific for
the extracellular domain of prostate-specific membrane antigen. Cancer research. 2000
Sep 15;60(18):5237-43.
31. Kinoshita Y, Kuratsukuri K, Landas S, Imaida K, Rovito Jr PM, Wang CY, Haas GP.
Expression of prostate-specific membrane antigen in normal and malignant human
tissues. World journal of surgery. 2006 Apr 1;30(4):628-36.
32. Murphy GP, Elgamal AA, Su SL, Bostwick DG, Holmes EH. Current evaluation of the
tissue localization and diagnostic utility of prostate specific membrane antigen. Cancer.
1998 Dec 1;83(11):2259-69.
33. Ghosh A, Heston WD. Tumor target prostate specific membrane antigen (PSMA) and its
regulation in prostate cancer. Journal of cellular biochemistry. 2004 Feb 15;91(3):528-39.
34. Perner S, Hofer MD, Kim R, Shah RB, Li H, Möller P, Hautmann RE, Gschwend JE,
Kuefer R, Rubin MA. Prostate-specific membrane antigen expression as a predictor of
prostate cancer progression. Human pathology. 2007 May 31;38(5):696-701.
35. Luthi-Carter R, Barczak AK, Speno H, Coyle JT. Molecular characterization of human
brain N-acetylated α-linked acidic dipeptidase (NAALADase). Journal of Pharmacology
and Experimental Therapeutics. 1998 Aug 1;286(2):1020-5.
36. Trover JK, Beckett ML, Wright GL. Detection and characterization of the prostate‐
specific membrane antigen (PSMA) in tissue extracts and body fluids. International
Journal of Cancer. 1995 Sep 4;62(5):552-8.
37. David KA, Milowsky MI, Kostakoglu L, Vallabhajosula S, Goldsmith SJ, Nanus DM,
Bander NH. Clinical utility of radiolabeled monoclonal antibodies in prostate cancer.
Clinical genitourinary cancer. 2006 Mar 31;4(4):249-56.
38. Milowsky MI, Nanus DM, Kostakoglu L, Vallabhajosula S, Goldsmith SJ, Bander NH.
Phase I trial of yttrium-90—labeled anti—prostate-specific membrane antigen
monoclonal antibody J591 for androgen-independent prostate cancer. Journal of clinical
oncology. 2004 Jul 1;22(13):2522-31.
39. Hillier SM, Maresca KP, Lu G, Merkin RD, Marquis JC, Zimmerman CN, Eckelman
WC, Joyal JL, Babich JW. 99mTc-labeled small-molecule inhibitors of prostate-specific
membrane antigen for molecular imaging of prostate cancer. Journal of Nuclear
Medicine. 2013 Aug 1;54(8):1369-76.
40. Reinfelder J, Kuwert T, Prante1 O, Wullich B, Hennig P, Beck M, Sanders J, Ritt P,
Schmidt D, Goebell P  First experience with PSMA-SPECT/CT using a 99mTc-labeled
PSMA inhibitor for patients with biochemical recurrence of prostate cancer J Nucl Med
May 1, 2015 vol. 56 no. supplement 3 67.

Clinical Protocol:  PyL-2301 
18F-DCFPyL 
Amendment 2: 06 Nov 2017 
Page 48 
41. Budaus L, Leyh-Bannurah SR, Salomon G et al. Initial experience of 68Ga-PSMA
PET/CT imaging in high-risk prostate cancer patients prior to radical prostatectomy. Eur
Urology 2015.
42. Eiber M, Maurer T, Souvatzoglou M, Beer AJ, Ruffani A, Haller B, Graner FP, Kübler
H, Haberkorn U, Eisenhut M, Wester HJ. Evaluation of hybrid 68Ga-PSMA ligand
PET/CT in 248 patients with biochemical recurrence after radical prostatectomy. Journal
of Nuclear Medicine. 2015 May 1;56(5):668-74.
43. Pfister D, Porres D, Heidenreich A, et al. Detection of recurrent prostate cancer lesions
before salvage lymphadenectomy is more accurate with 68Ga-PSMA-HBED-CC than
with 18F-Fluoroethylcholine PET/CT. European Journal of Nuclear Medicine and
Molecular Imaging. 2016 Mar 19:1-8.
44. Bluemel C, Krebs M, Polat B et al. 68Ga-PSMA PET/CT in patients with biochemical
prostate cancer recurrence and negative 18F-choline PET/CT. Clin Nucl Med 2016.
45. Dietlein M, Kobe C, Kuhnert G, Stockter S, Fischer T, Schomäcker K, Schmidt M,
Dietlein F, Zlatopolskiy BD, Krapf P, Richarz R. Comparison of [18F] DCFPyL and
[68Ga] Ga-PSMA-HBED-CC for PSMA-PET Imaging in Patients with Relapsed Prostate
Cancer. Molecular Imaging and Biology. 2015 Aug 1;17(4):575-84.
46. Chen Y, Pullambhatla M, Foss CA, Byun Y, Nimmagadda S, Senthamizhchelvan S,
Sgouros G, Mease RC, Pomper MG. 2-(3-{1-Carboxy-5-[(6-[18F] fluoro-pyridine-3-
carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid,[ 18F] DCFPyL, a PSMA-based PET
imaging agent for prostate cancer. Clin Cancer Res. 2011 Dec 15;17(24):7645-53.
47. Recent Updates to NCCN Clinical Practice Guidelines in Oncology (NCCN
Guidelines®).  NCCN website.
https://www.nccn.org/professionals/physician_gls/recently_updated.asp Accessed July
12, 2016.
48. Fleiss JL, Levin B, Paik MC. The Measurement of interrater agreement. In: Statistical
methods for rates and proportions. 3rd Ed. New York, NY: Wiley, 2003;29-33
49. Gönen M, Panageas KS, Larson SM. Statistical issues in analysis of diagnostic Imaging
experiments with multiple observations per patient. Radiology 2001; 221:763-767