Conditions: Prostatic Neoplasms Prostate Cancer
Keywords: Prostate Specific Membrane Antigen Radiolabeled PET Agent Imaging NaF
Allocation: NON_RANDOMIZED | Intervention model: PARALLEL
Enrollment: 116
Healthy volunteers: no

Brief summary:
Background:

\- Prostate cancer is the second leading cause of cancer deaths in American men. A chemical called a radiotracer helps doctors get images of this type of cancer. Researchers want to test a radiotracer called N-\[N-\[(S)-1,3-dicarboxypropyl\]carbamoyl\]-4-(18)F-fluorobenzyl-L-cysteine ((18)F-DCFBC) (18F-DCFBC).

Objective:

\- To see if the radiotracer 18F-DCFBC can identify sites of prostate cancer in the body.

Eligibility:

\- Men ages 18 and over with prostate cancer. The cancer must be newly diagnosed, have relapsed, or has spread outside the prostate.

Design:

* Participants will be screened with physical exam and medical history. They will give a blood sample.
* Participants will be divided into three groups.

Group 1: people with cancer only in the prostate scheduled for surgical prostate removal or biopsy at National Institutes of Health (NIH).

Group 2: people who had their prostate removed or had radiation therapy and now have a rising prostate-specific antigen (PSA) without other signs of disease.

Group 3: people whose cancer has spread to other areas of the body.

* Participants will have 18F-DCFBC injected into a vein then imaged in a positron emission tomography (PET)/computed tomography (CT) camera. During the scans, they will lie on their back on the scanner table.
* Group 1 will have a magnetic resonance imaging (MRI) scan. A tube will be placed in the rectum. Coils may be wrapped around the outside of the pelvis. Participants will have a contrast agent injected through an intravenous line.
* Group 3 will have another PET/CT scan with a different radiotracer, 18F NaF, within 21 days of the 18F-DCFBC scan to look for prostate cancer in the bone.
* Group 3 will repeat the two PET/CT scans 4-6 months after the initial scans.
* A few days after each scan, participants will be contacted for follow-up.

Detailed description:
Background

* Prostate cancer is the second leading cause of cancer deaths in American men.
* Current methods of imaging advanced prostate cancer (computed tomography ((CT) and bone scan) are non specific and new, more specific molecular imaging probes are sought.
* Many prostate cancers express the prostate specific membrane antigen (PSMA) a transmembrane protein with N-acetylated alpha-linked acidic dipeptidase (NAALADase) enzymatic activity. PSMA is also expressed in angiogenesis but otherwise has limited expression in normal tissue.
* N-\[N-\[(S)-1,3-dicarboxypropyl\]carbamoyl\]-4-(18)F-fluorobenzyl-L-cysteine ((18)F-DCFBC) (18F-DCFBC) is a radiolabeled positron emission tomography (PET) agent which binds with high affinity to PSMA and through whole-body non-invasive functional imaging, may provide new information on the expression of PSMA.

Primary Objective

\- To assess the ability of 18F-DCFBC to differentiate between tumorous and nontumorous tissues in localized, recurrent (based on rising prostatic-specific antigen ((PSA) post treatment) and metastatic prostate cancer

Eligibility

* Subject is greater than or equal to 18 years old
* Eastern Cooperative Oncology Group (ECOG) 0-2 with adenocarcinoma of the prostate and fits criteria for one of the following:
* ARM 1

  \-- Patients with known localized prostate cancer with a soft tissue lesion at least 6mm or greater.

  ---A multiparametric magnetic resonance imaging (MRI) (standard of care at the National Institutes of Health ((NIH) Clinical Center) must be performed within 4 months of18F-DCFBC injection with findings suggestive for prostate cancer and confirmed with histopathology.
* ARM 2

  * Patients with biochemical prostate cancer relapse after definitive treatment

    * For patients status post radiation therapy for prostate cancer, a PSA increase from post radiation therapy nadir
    * OR
    * For patients status post prostatectomy, any PSA \>/=0.2 ng/ml
  * Nonspecific or no evidence for disease on standard imaging modality
* ARM 3

  * Patients with identifiable metastatic disease on a conventional imaging modality. If only soft tissue metastasis, one lesion must measure 6mm or greater. Patients must have confirmation of prostate cancer prior to 18F-DCFBC imaging.

Design

This is a single site 3-arm study enrolling a total of 110 evaluable patients: Arm 1 will include 12 patients with presumed localized prostate cancer scheduled to undergo prostatectomy or biopsy within 4 months of enrollment; Arm 2 will include 78 patients with biochemical recurrence without evidence of metastasis on conventional imaging; and Arm 3 will include 20 patients with known metastatic disease who may or may not be on or/scheduled to begin therapeutic intervention. Patients with presumed localized disease will undergo a standard of care, clinical multiparametric endorectal coil MRI in the National Cancer Institute (NCI) Molecular Imaging Clinic within 4 months of screening. Patients in Arm 3 will undergo 2 imaging sessions: baseline and 4-6 month follow-up. Clinical records (including PSA) and treatment (if any) that occurred in the imaging interval must be available. All patients in Arm 3 will also undergo Na18F PET/CT for evaluation of bone metastases as part of this protocol. In order to allow for a small number of nonevaluable patients, the accrual ceiling will be set at 125.

Arms:
arm 1: Patients with known localized prostate cancer with a soft tissue lesion at least 6mm or greater. arm 2: Patients with biochemical prostate cancer relapse after definitive treatment arm 3: Patients with identifiable metastatic disease on a conventional imaging modality. If only soft tissue metastasis, one lesion must measure 6mm or greater. Patients must have confirmation of prostate cancer prior to investigational imaging.

Interventions: intervention 1: 18F DCFBC intervention 2: Sodium (Na)18F positron emission tomography (PET)/computed tomography (CT)
Intervention descriptions: intervention 1: Each subject will receive a single intravenous (i.v.) dose of 18F DCFBC by bolus injection at a rate of approximately 1 ml/3-5 sec. intervention 2: None

Protocol document:
Prot_SAP_000.pdf: 
 
 
 
 
CC Protocol Number: 14-C-0140E 
Title of Study: A Pilot Study of 18F-DCFBC PET/CT in Prostate Cancer 
Abbreviated Title: DCFBC in prostate cancer 
Version date: 10/27/2015 
CIP #: 9622 
Amendment E 
Principal Investigator:   
Maria Liza Lindenberg, MD 
Molecular Imaging Program (MIP), CCR/NCI  
Bldg 10/ RMB3B403  
Bethesda, MD 20892 
301-443-0604 
liza.lindenberg@mail.nih.gov 
Lead Associate Investigator:  Peter L. Choyke, MD, 
MIP, CCR/ NCI  
Building 10, Room 1B40  
Bethesda, MD 20892 
301-451-4220 
pchoyke@nih.gov 
Associate Investigators: 
  Karen A. Kurdziel, MD 
MIP/ CCR/NCI 
Bldg 10/ RmB3B403 
Bethesda, MD 20892 
301-443-0622 
karen.kurdziel@nih.gov 
Ismail Baris Turkbey, MD,  
MIP, CCR/NCI 
Building 10/ Room B3B69F 
Bethesda, MD 20892 
turkbeyi@mail.nih.gov 
William Dahut, MD,  
Genitourinary Malignancy Branch (GMB)/ CCR/NCI 
Building 10, Room 13N240E 
Bethesda, MD 20892 
301-435-8183 
dahutw@mail.nih.gov  
Peter Pinto, M.D. 
Urologic Oncology Branch 
10-CRC - Hatfield Clinical Research Center, 2-5952 
Bethesda, MD 20892 
pp173u@nih.gov 
James Gulley, MD, PhD 
GMB/CCR/NCI 
Building 10, Rm 13N208 
Bethesda, MD 20892 


CC Protocol Number: 
14-C-0140 
Abbreviated Title: DCFBC in prostate cancer 
Version date: 10/27/2015 
CIP #: 9622 
2 
301- 435-2956 
gulleyj@mail.nih.gov 
Ravi Madan, MD 
GMB/CCR/NCI 
Building 10, Rm 13N208 
Bethesda, MD 20892 
301- 496-3493 
madanr@mail.nih.gov 
Deborah Citrin, MD,  
ROB/ CCR/ NCI 
Building 10-CRC Room b2-3500 
Bethesda MD 20892 
citrind@mail.nih.gov 
Bradford Wood, MD,  
Director, Center for Interventional Oncology 
Chief, Interventional Radiology 
NIH Clinical Center 
9000 Rockville Pike 
Building 10, Room 1C341 
Bethesda, MD 20892 
Maria Merino, M.D.*  
Laboratory of Pathology/ NCI 
Building 10 - Room 2N212 
Bethesda, MD 20892 
mjmerino@box-m.nih.gov  
 
Mark Ahlman, MD, 
Radiology and Imaging Sciences 
Bldg 10, Clinical Center 
Bethesda MD 20892 
ahlmanma@mail.nih.gov 
 
Ashkan Malayeri, MD,  
Radiology and Imaging Sciences 
Bldg 10, Clinical Center 
Bethesda MD 20892 
malayeriaa@mail.nih.gov  
 
Yolanda McKinney, RN,  
Office of the Clinical Director (OCD), CCR/NCI 
Building 10/ Room B3B69E 
Bethesda, MD 20892 
301-443-6913 
ymckinney@mail.nih.gov 
 


CC Protocol Number: 
14-C-0140 
Abbreviated Title: DCFBC in prostate cancer 
Version date: 10/27/2015 
CIP #: 9622 
3 
Stephen Adler, Ph.D.* 
Leidos Biomed Contractor, MIP CCR/NCI 
Building 10, Room B3B69 
Bethesda, MD 20892 
301-451-4220 
sadler@mail.nih.gov 
 
Paula Jacobs PhD., CIP/DCTD/NCI 
9609 Medical Center Dr., MSC 9729 
Rockville, MD 20892-9729 
Tel: 240-276-5950 
jacobsp@mail.nih.gov  
 
Statistician: 
Joanna H. Shih, Ph.D.* 
Biometric Research Branch 
Division of Cancer Treatment and Diagnosis 
National Cancer Institute  
9609 Medical Center Dr., MSC 9735 
Rockville, MD 20892-9735 
Phone: 240-276-6035 
jshih@mail.nih.gov 
 
Referral Contact:  
 
 
Yolanda McKinney, RN,  
OCD, CCR/NCI 
Building 10/ Room B3B69E 
Bethesda, MD 20892 
301-443-6913 
ymckinney@mail.nih.gov 
  
* Indicates Associate Investigators who will not be involved in clinical decisions or 18F-
DCFBC ordering. 
Study Sponsor: National Cancer Institute, Cancer Imaging Program 
IND #:  122053 
NCI-Supplied Agent(s):  18F-DCFBC  
Other Agent(s):  18F NaF  
Manufacturer: Leidos Biomedical Research, Inc. 


CC Protocol Number: 
14-C-0140 
Abbreviated Title: DCFBC in prostate cancer 
Version date: 10/27/2015 
CIP #: 9622 
4 
Précis  
Background 
• Prostate cancer is the second leading cause of cancer deaths in American men 
• Current methods of imaging advanced prostate cancer (CT and bone scan) are non-
specific and new, more specific molecular imaging probes are sought. 
• Many prostate cancers express the prostate specific membrane antigen (PSMA) a 
transmembrane protein with NAALADase enzymatic activity.  PSMA is also 
expressed in angiogenesis but otherwise has limited expression in normal tissue. 
• 
18F-DCFBC is a radiolabeled PET agent which binds with high affinity to PSMA 
and through whole-body non-invasive functional imaging, may provide new 
information on the expression of PSMA. 
Primary Objective 
• To assess the ability of 18F-DCFBC to differentiate between tumorous and non-
tumorous tissues in localized, recurrent (based on rising PSA post treatment) and 
metastatic prostate cancer  
Eligibility 
• Subject is  ≥18 years old 
• ECOG 0-2 with adenocarcinoma of the prostate and fits criteria for one of the 
following:  
• ARM 1 
o Patients with known localized prostate cancer with a soft tissue lesion 
at least 6mm or greater. 
 A multiparametric MRI (standard of care at the NIH Clinical 
Center) must be performed within 4 months of18F-DCFBC  
injection with findings suggestive for prostate cancer and 
confirmed with histopathology. 
• ARM 2 
o Patients with biochemical prostate cancer relapse after definitive 
treatment  
 For patients status post radiation therapy for prostate cancer, 
any PSA increase from post radiation therapy nadir 
OR 
 For patients status post prostatectomy, a PSA >/=0.2 ng/ml  
o Nonspecific or no evidence for disease on standard imaging modality 
• ARM 3 
o Patients with identifiable metastatic disease on a conventional imaging 
modality. If only soft tissue metastasis, one lesion must measure 6mm 
or greater. Patients must have confirmation of prostate cancer prior to 
18F-DCFBCimaging. 
Design 


CC Protocol Number: 
14-C-0140 
Abbreviated Title: DCFBC in prostate cancer 
Version date: 10/27/2015 
CIP #: 9622 
5 
This is a single site 3-arm study enrolling a total of  110 evaluable patients:  Arm 1 will 
include 12 patients with presumed localized prostate cancer scheduled to undergo 
prostatectomy or biopsy within 4 months of enrollment; Arm 2 will include 78 patients with 
biochemical recurrence without evidence of metastasis on conventional imaging; and Arm 3 
will include  20 patients with known metastatic disease who may or may not be on 
or/scheduled to begin therapeutic intervention. Patients with presumed localized disease will 
undergo a standard of care, clinical multiparametric endorectal coil MRI in the NCI 
Molecular Imaging Clinic within 4 months of screening. Patients in Arm 3 will undergo 2 
imaging sessions: baseline and 4-6 month follow-up. Clinical records (including PSA) and 
treatment (if any) that occurred in the imaging interval must be available. All patients in Arm 
3 will also undergo Na18F PET/CT for evaluation of bone metastases as part of this protocol. 
In order to allow for a small number of nonevaluable patients, the accrual ceiling will be set at 
125. 


CC Protocol Number: 
14-C-0140 
Abbreviated Title: DCFBC in prostate cancer 
Version date: 10/27/2015 
CIP #: 9622 
6 
Imaging Schema 
ARM 1 Suspected localized prostate cancer  
 
*Biopsy is standard of care at NCI, prostatectomy will only be performed if clinically 
indicated and patient wishes to pursue this form of treatment 
ARM 2 (biochemical recurrence) 
 
ARM 3 (known metastasis)  
 
Each set of Na18F PET/CT and 18F-DCFBC PET/CT will be done within 3-weeks of each 
other. 
Multiparametric 
MRI at NCI 
(within 4 mo) 
18F-DCFBC 
PET/CT 
Biopsy or 
Prostatectomy 
(within 4 mo) 
Correlation with 
histopathology  
Suspected 
recurrence 
(PSA↑) 
18F-DCFBC 
PET/CT 
Correlation with 
conventional imaging 
and biopsy when 
possible or other clinical 
data within 12 months 
Metastatic 
disease 
seen on 
imaging 
modality 
PET/CT: 
 *Na18F  
*18F-DCFBC   
Optional 
Treatment  
(not designated 
by this protocol) 
 
Follow-up PET/CTs 
in  4-6 months 
*Na18F  
*18F-DCFBC  
 
 
Correlation 
with  
conventional 
imaging  
and/or other 
clinical data 


CC Protocol Number: 
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Abbreviated Title: DCFBC in prostate cancer 
Version date: 10/27/2015 
CIP #: 9622 
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TABLE OF CONTENTS 
Summary of Changes .............................................................................................................. iv 
Protocol ..................................................................................................................................... iv 
Précis .......................................................................................................................................... 4 
Background ............................................................................................................................... 4 
TABLE OF CONTENTS ......................................................................................................... 7 
1 
Study Objectives ............................................................................................................. 10 
1.1 
Primary Objective .................................................................................................... 10 
1.2 
Secondary Objectives............................................................................................... 10 
1.3 
Exploratory Objective ............................................................................................. 10 
2 
Background and Rationale ............................................................................................ 10 
2.1 
Prostate Cancer ........................................................................................................ 10 
2.2 
18F DCFBC (CIP # 122053) ..................................................................................... 12 
2.3 
Rationale ................................................................................................................... 16 
3 
PATIENT SELECTION ................................................................................................ 18 
3.1 
Eligibility Criteria .................................................................................................... 18 
3.2 
Exclusion Criteria .................................................................................................... 19 
3.3 
Screening Evaluation ............................................................................................... 19 
3.4 
Inclusion of Women and Minorities ....................................................................... 20 
3.5 
Registration Procedures .......................................................................................... 20 
4 
STUDY IMPLEMENTATION ..................................................................................... 20 
4.1 
Study Design ............................................................................................................. 20 
4.2 
Stratification Procedures ......................................................................................... 21 
4.3 
Drug Administration ............................................................................................... 21 
4.4 
18F DCFBC PET/CT Imaging ................................................................................. 21 
4.5 
18F NaF PET/CT Imaging ....................................................................................... 23 
4.6 
Additional Imaging .................................................................................................. 24 
4.7 
Pathology .................................................................................................................. 24 
4.8 
Biopsy ........................................................................................................................ 24 
4.9 
Correlative Studies................................................................................................... 24 
4.10 
Off-Study Criteria ................................................................................................ 26 
4.11 
Follow-up ............................................................................................................... 27 
5 
Dose Modifications ......................................................................................................... 27 


CC Protocol Number: 
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Abbreviated Title: DCFBC in prostate cancer 
Version date: 10/27/2015 
CIP #: 9622 
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6 
ADVERSE EVENTS:  LIST AND REPORTING REQUIREMENTS ..................... 27 
6.1 
Comprehensive Adverse Events and Potential Risks List (CAEPR) .................. 27 
6.2 
Expedited Adverse Event Reporting to CTEP ...................................................... 28 
6.3 
Routine Adverse Event Reporting to CTEP .......................................................... 29 
6.4 
Secondary Malignancy ............................................................................................ 29 
6.5 
Second Malignancy .................................................................................................. 30 
7 
PHARMACEUTICAL INFORMATION .................................................................... 30 
7.1 
18F DCFBC (CIP # 122053) .................................................................................... 30 
7.2 
18F NaF Source: ........................................................................................................ 33 
8 
Study Calendar ............................................................................................................... 33 
8.2 
Surgical Guidelines .................................................................................................. 38 
8.3 
Radiation Therapy Guidelines ................................................................................ 38 
9 
DATA REPORTING / REGULATORY REQUIREMENTS .................................... 39 
9.1 
Data Reporting ......................................................................................................... 39 
10 Cooperative Research and Development Agreement (CRADA) / Clinical Trials 
Agreement (CTA) ................................................................................................................... 39 
11 CONCOMITANT MEDICATION/MEASURES ........................................................ 39 
12 DATA COLLECTION AND EVALUATION ............................................................. 39 
12.1 
Data Collection ..................................................................................................... 39 
12.2 
Toxicity Criteria ................................................................................................... 41 
13 Biospecimen Collection .................................................................................................. 41 
13.1 
Tissue Samples (Arm 1) ....................................................................................... 41 
13.2 
Blood Samples ....................................................................................................... 42 
14 STATISTICAL CONSIDERATIONS .......................................................................... 42 
14.1 
Primary Analysis .................................................................................................. 42 
14.2 
Secondary Analysis .............................................................................................. 43 
14.3 
Interim Futility Analysis and Early Stopping Rule .......................................... 43 
14.4 
Sample Size and Accrual Rate ............................................................................ 43 
15 SAFETY REPORTING REQUIREMENTS/DATA AND SAFETY MONITORING 
PLAN for NCI IRB ................................................................................................................. 44 
15.1 
Definitions ............................................................................................................. 44 
15.2 
NCI-IRB Reporting .............................................................................................. 45 
15.3 
NCI-IRB Requirements for PI Reporting at Continuing Review .................... 45 
15.4 
Data and Safety Monitoring Plan ....................................................................... 46 


CC Protocol Number: 
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Abbreviated Title: DCFBC in prostate cancer 
Version date: 10/27/2015 
CIP #: 9622 
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16 HUMAN SUBJECTS PROTECTION.......................................................................... 47 
16.1 
Rationale for Subject Selection ........................................................................... 47 
16.2 
Participation of Children ..................................................................................... 47 
16.3 
Evaluation of Benefits and Risks/Discomforts................................................... 47 
16.4 
Risks/Benefits Analysis ........................................................................................ 47 
16.5 
Consent and Assent Process and Documentation.............................................. 48 
17 References ........................................................................................................................ 49 
18 APPENDICES ................................................................................................................. 51 
18.1 
APPENDIX A: Performance Status Criteria .................................................... 51 
18.2 
Appendix B: F18 DCFBC Order Form .............................................................. 52 
 
 


CC Protocol Number: 
14-C-0140 
Abbreviated Title: DCFBC in prostate cancer 
Version date: 10/27/2015 
CIP #: 9622 
10 
1 
Study Objectives 
1.1 
Primary Objective 
 
• To assess the ability of 18F-DCFBC to differentiate between tumorous and non-
tumorous tissues in localized, recurrent (based on rising PSA post treatment) and 
metastatic prostate cancer   
1.2 
Secondary Objectives 
• Compare the distribution 18F-DCFBC with multiparametric MRI and whole mount 
histopathology in patients undergoing prostatectomy 
• Evaluate the distribution 18F-DCFBC uptake in prostate cancer patients with 
biochemical relapse (site of recurrence unknown) 
• Compare focal 18F-DCFBC uptake with focal abnormalities identified on standard of 
care imaging 
• Compare the uptake of 18F-DCFBC in bone with respect to Na18F PET/CT in patients 
with metastatic disease (the emerging gold standard, for detection of bony metastases). 
• Evaluate the change over time in 18F-DCFBC distribution in patients with known 
metastatic disease with clinical follow-up data 4-6 months post baseline 18F-DCFBC 
PET/CT (e.g. understand the effect of androgen deprivation therapy (ADT) on 18F-
DCFBC uptake) 
1.3 
Exploratory Objective 
• If PET/MRI is obtained, findings will be compared with other acquired imaging 
studies. 
 
2 
Background and Rationale 
2.1 
Prostate Cancer 
The lifetime risk of developing prostate cancer for men is 1 in 6. In 2013, it is estimated that 
238,590 men will be diagnosed with and 29,720 men will die of cancer of the prostate 
according to the National Cancer Institute. Many therapeutic options are dependent on the 
cancer stage at diagnosis and after treatment, recurrent malignancy and accurately defining 
these stages can be diagnostically challenging. Especially complex is the patient with 
biochemical recurrence who has no other evidence for cancer except for a suspiciously rising 
PSA. Accurate assessment at all levels of the disease is critical to guide the best therapy and 
minimize morbidity related to treatment. Non-invasive methods to detect and monitor this 
malignancy are limited to PSA for biochemical relapse and CT, US and MRI for standard 
anatomic morphology. Nuclear medicine has the potential to capture physiologic function but 
is currently limited to conventional 99mTc MDP bone scintigraphy or18F NaF PET/CT, which 
is restricted to visualizing bone changes; however the findings can be nonspecific, occur from 
metastatic disease or benign causes. The only FDA approved molecular imaging radiotracer to 
detect soft tissue prostate cancer metastasis, 111In Prostascint, has proven to be suboptimal for 
many reasons and is not routinely used in most clinical settings.  Improving molecular 
imaging capabilities in prostate cancer is crucial to battling this illness. 


CC Protocol Number: 
14-C-0140 
Abbreviated Title: DCFBC in prostate cancer 
Version date: 10/27/2015 
CIP #: 9622 
11 
Much interest has centered on prostate specific membrane antigen (PSMA) as a target for 
imaging and therapy.  Also known as Glutamate Carboxypeptidase II (GCPII) in the central 
nervous system, PSMA is a type II cell surface membrane glycoprotein receptor found in 
almost all prostate cancers, especially in advanced, hormone-independent and metastatic 
disease. It can also be found in the neovasculature of nearly all solid tumors. [1, 2] It is also 
seen in normal prostate, small bowel, proximal renal tubules, salivary glands and brain but at 
100 to 1000 fold lower expression. [3] This normal expression  appears to occur within 
luminal sites which is advantageous in formulating specialized antibodies because they do not 
need to cross intact basement membranes and tight junctions to bind.  Another attractive 
feature of PSMA is that it does not appear to be secreted in serum, unlike PSA [4]; therefore 
imaging background due to organ perfusion will be less of an issue. Important to drug 
development, PSMA bound antibodies undergo internalization through clathrin coated pits. 
[5] This would give time for targeted imaging once any background activity and non-specific 
binding clears. These unique characteristics make PSMA a desirable target.  
Monoclonal antibodies have been developed against PSMA, but the first agent, 111In 
Prostascint, targets an intracellular epitope that is inaccessible in viable tumor cells which is 
one factor contributing to its lack of clinical utility.[6] More promising antibodies have been 
engineered with binding sites to the extracellular domain such as J591 and IgG monoclonal 
antibodies such as 64Cu-3/A12. [7] 
J591 is the first humanized monoclonal antibody targeting the extracellular domain of PSMA 
to be tested in humans.  In one trial, 29 patients received 111In-J591 for imaging followed by 
90Y-J591 for therapy. In the parallel trial, 24 patients were treated with 177Lu-J591, an isotope 
that can be imaged directly. Overall, of the 43 evaluable patients J591 accurately targeted 
bone and/or soft tissue lesions in 42 patients (98%). J591 accurately targeted bone lesions in 
32 of 34 (94%) and soft tissue lesions in 13 of 18 (72%) evaluable patients. [8] Nargund et al 
used PSMA scintigraphy with 99mTc labeled J591 to show usefulness in detecting prostate bed 
recurrence and distant micrometastasis but not in identifying tumors of the capsule, seminal 
vesicles or bladder neck.[9] Imaging through PET has been accomplished using 64Cu -J591. 
Evans et al demonstrated that the androgen receptor (AR) is required for androgen repression 
of PSMA and can be quantitatively imaged with PET. [10] Androgen deprivation therapies, 
such as MDV3100, increase 64Cu -J591 uptake.  Illustrating AR signaling changes from 
pharmacologic intervention in human prostate cancer xenograft models suggests this 
radiotracer’s potential as an imaging biomarker of AR activity.   
Disadvantages of radiolabelled antibodies include their large size which slows clearance from 
the blood pool producing high background radioactivity. The bulky size could also prevent 
contact with all available binding sites of a heterogeneous tumor. Consequently, binding to 
target tumor is not quick and can take several days.  Small molecule PSMA inhibitors have 
been created to address this shortcoming.  Low-molecular weight compounds have better 
pharmacokinetics with faster clearance from nontarget tissues and short circulation times in 


CC Protocol Number: 
14-C-0140 
Abbreviated Title: DCFBC in prostate cancer 
Version date: 10/27/2015 
CIP #: 9622 
12 
the blood pool. Typically, these compounds bind to zinc and attach to a glutamate form and 
belong to 3 different classes- (1) phosphonate-, phosphate-, and phosphoramidate, (2) thiols or 
(3) ureas.   
Urea based scaffolds have yielded the most promising results for molecular imaging. Foss et 
al first synthesized urea-based small molecule PSMA ligands for PET, 11C-DCMC, and 
SPECT, 125I-DCIT, and showed specific binding to PSMA in prostate cancer xenograft rodent 
models.[11] The PET agent has limited clinical use due to the short half-life of 20 minutes 
for11C.  125I is produced by nuclear reactor and, with a long half-life (59.4 days) and low 
energy emissions (27keV) it is suboptimal as an imaging agent. Substitution with 123I 
(cyclotron produced, primary emission 159keV, half-life of 13.2 days), while imagable with a 
gamma camera/SPECT, given current limitations SPECT camera yields non-quantitative 
images with high count loss. 68Ga PSMA ligands to urea compounds have also been produced 
with good PSMA affinity and tumor-to-background ratios.[12] and can be imaged by 
PET/CT. A valuable feature of 68Ga-PSMA compounds is that it is a generator produced 
radiotracer with a reasonable half-life (68 minutes), eliminating the need for a cyclotron and 
therefore could be more widely available for use.  
A significant urea platform for radiolabelling is a lysine glutamate urea molecule and its tri-
esters.  SPECT agents have been produced from these foundations (123I-MIP-1072 and 123I-
MIP-1095), that have good affinity for PSMA and are able to detect metastatic lesions. [13] 
Structurally similar, Mease et al expanded  initial work with carbon-11–labeled compound N-
[N-[(S)-1,3-dicarboxypropyl]carbamoyl]- S-[11C]methyl-L-cysteine (11C-DCMC) to 
developing fluorine-18, N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-4- [18F]fluorobenzyl-L-
cysteine (18F-DCFBC) as the first agent designed specifically for clinical PET imaging of 
prostate cancer.[14] 
2.2 
18F DCFBC (CIP # 122053) 
18F DCFBC is a small molecule targeting an external binding domain of PSMA. Mease et al 
described the synthesis, in vivo behavior and human dosimetry estimates using mouse 
biodistribution data for 18F DCFBC.[14] Mice were implanted with PSMA+ and PSMA – 
prostate cancer cell lines and injected with 18F DCFBC. PSMA has N-acetylaspartyl-
glutamate (NAAG) peptidase activity which was utilized to determine 18F DCFBC’s 
inhibitory capacity for PSMA through the NAAG peptidase inhibition assay. Findings of 13.9 
nmol/L for IC50 value were consistent with other compounds of this class.  At 60 minutes 
after radiotracer injection, rodents had the highest uptake in the kidneys and urinary bladder 
as well as in the PSMA+ tumor.  Little to no uptake was noted in PSMA- cells. Physiologic 


CC Protocol Number: 
14-C-0140 
Abbreviated Title: DCFBC in prostate cancer 
Version date: 10/27/2015 
CIP #: 9622 
13 
excretion occurred through the kidneys and bladder and by 2 hours, renal radioactivity was 
confined to the cortex.  Target to muscle background ratio of 10:1 at 60 min and 20:1 was 
seen at 120 min after injection. Clearance from non-target tissue was faster than from target 
sites.  Low uptake in normal bone was noted indicating no significant defluorination of 18F 
DCFBC, which will allow visualization of bone metastasis.  
Their human dosimetry estimates based on the animal model [14] calculate the highest 
absorbed dose to the kidneys at 0.0487 mGy/MBq (0.2 rad/mCi).  The mean absorbed dose to 
the liver was 0.009 mGy/MBq and .0005 mGy/MBq to the brain. The effective dose 
equivalent was .005 mSv/MBq and the effective dose was .003 mSv/MBq. Administering a 
dose of 185 to 370 MBq (5-10 mCi) 18F DCFBC yields acceptable absorbed dose estimates 
for nuclear medicine diagnostic procedures.  
Cho et al followed up with initial clinical experience with 18F DCFBC in metastatic prostate 
cancer patients.[15] Five patients with metastatic disease were injected with 370 MBq (10 
mCi) of 18F DCFBC and serial PET/CTs obtained for 2 hours after injection.  Based on visual 
and quantitative assessment, the highest ratio of tumor activity to background was seen at the 
2 hour scan. PET images were considered positive if focal radioactivity was above adjacent 
background tissue or blood pool for lymph nodes or bone.  Lean body mass maximum 
standardized uptake values (SUVmax) were obtained for regions-of-interest (ROIs) for 
quantitative measurements.  Focal abnormal PET uptake was seen in 32 metastatic lymph 
nodes and bone lesions with median SUVmax  of 5.6 for lymph nodes, and 3.6 for bone. 
Conventional imaging was concordant with PET findings in 21 sites, 5 of them bone. 
Discordant positive PET findings were attributed to possible early bone metastases or 
subcentimeter lymph nodes. All 10 positive sites on conventional imaging that were negative 
on PET, were in bone and considered indeterminate for malignancy or due to trauma. One 
true metastatic bone lesion that was PET negative could have been related to antiandrogen 
therapy.   
Metabolite analysis was also done in 2 patients with high performance liquid chromatography 
with essentially no metabolism or defluorination of 18F DCFBC in plasma at approximately 1 
and 2 hours after injection.  Radioactivity remained almost entirely within the blood plasma. 
Surprisingly, blood pool activity remained moderately persistent through imaging. Possible 
explanations include binding to a free form of PSMA circulating in the blood. They tested the 
inhibitory capacity of unlabeled DCFBC to prevent PSMA from hydrolyzing N-acetylated 
aspartyl-glutamate in normal human plasma and found 3nM was the 50% inhibitory 
concentration. 
Dosimetry calculations showed a mean effective dose of 19.9 + 1.34 uSv/MBq.  The highest 
mean absorbed dose (uGy/MBq) was the urinary bladder wall (32.4) then the stomach wall 


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Abbreviated Title: DCFBC in prostate cancer 
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CIP #: 9622 
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(30.2), heart wall (29.2) and kidneys (28.4). Similar to preclinical findings, 18F DCFBC, 
cleared through urinary excretion with PSMA-mediated uptake in normal renal tissue.  No 
significant brain uptake was noted consistent with the radiotracer’s hydrophilic nature (and 
resultant inability to cross the blood-brain barrier).  Effective dose estimates are comparable 
to 18F FDG (used in clinic routinely) which is 1.90 x 10-2 mSv/MBq and 18F DCFBC averages 
1.99 x 10-2 mSv/MBq per administered dose.  Their dosimetry calculations are below. 
 
Figure 1: Average Organ-Absorbed Dose (mGy/MBq) and Estimated Effective Dose 
(mSv/MBq) [15] 
In this study, none of the 5 patients experienced any severe adverse events. There were 3 
minor adverse events that were classified as either unrelated or unlikely to be attributable to 
the radiopharmaceutical. Two patients experienced grade 3 blood pressure events using the 
Common Terminology Criteria for Adverse Events (National Cancer Institute) on routine vital 
sign assessment after administration of the radiopharmaceutical (patient 1 unrelated; patient 2 
unlikely), both of which resolved on 7-d follow-up assessment. Several days after 
administration of the radiopharmaceutical, a third patient experienced lower back pain that 
began during physical exertion and was considered unrelated to the radiopharmaceutical. 


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Figure 2 18F-DCFBC PET anterior projection maximal-intensity-projection images at 2 h 
after injection in patient 1, with several bone metastases (arrow) (A), and patient 5, 
with LN metastases (arrow) (B), as confirmed by correlation to CT portion of 
PET/CT exam. [15] 
2.2.1 Toxicity and Pharmacology 
2.2.1.1 Toxicity in animals 
A toxicity report “Single Dose Toxicity Study of 19F-DCFBC (NSC-743104) in Rats” was 
prepared by Bridge GPS, Inc. (Study No. 1535-07015). The following summary is taken from 
that report. 
This study was designed to determine target organ toxicity of 19F-DCFBC (NSC-743104) 
and its reversibility in rats treated with a single intravenous dose. 
Sixty Fischer 344 rats (30/sex) were randomly assigned to one of three dose 
groups(10/sex/group) based on body weight and physical examination. Five rats/sex/group 
were designated to the main phase of the study, and five rats/sex/group were designated to the 
recovery phase of the study. All animals were dosed once on Study Day (SC) 1 via 
intravenous injection (tail vein) with either the control article (5% dextrose) or 19F-DCFBC 
(NSC-743104) at nominal dose levels of 0.1 or 0.5 mg/kg. Terminal sacrifice necropsies were 
performed on SD 4; recovery sacrifice necropsies were performed on SD 15.Parameters 
evaluated during the study included mortality, clinical and cage side observations, body 
weights, body weight changes, clinical pathology parameters (clinical chemistry and 
hematology), gross pathology and histopathology. Mortality, clinical and cage-side 
observation, body weight and body weight changes, clinical pathology, gross pathology and 
histopathology were unaffected by treatment. 
Based on the results of this study, a single intravenous injection of 18F-DCFBC (NSC-
743104) at doses up to 0.5 mg/kg to male and female Fischer 344 rats was well tolerated. 


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Abbreviated Title: DCFBC in prostate cancer 
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CIP #: 9622 
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2.2.1.2 Toxicity in Humans 
Cho et al [15] studied five patients with metastatic prostate cancer and none experienced any 
severe adverse events. There were 3 adverse events that were classified as either unrelated or 
unlikely to be attributable to the radiopharmaceutical. Two patients experienced grade 3 blood 
pressure events using the Common Terminology Criteria for Adverse Events (National 
Cancer Institute) on routine vital sign assessment after administration of the 
radiopharmaceutical (patient 1 unrelated; patient 2 unlikely), both of which resolved on 7-d 
follow-up assessment. Several days after administration of the radiopharmaceutical, a third 
patient experienced lower back pain that began during physical exertion and was considered 
unrelated to the radiopharmaceutical. 
2.2.2 Safety  
Cho et al [15] demonstrated that radiation doses to patients with 18F DCFBC are comparable 
to other PET radiopharmaceuticals such as 18F FDG with the overall effective dose for 18F-
DCFBC averaging 1.99 × 10−2 mSv/MBq per administered dose (vs. 18F-FDG, estimated at 
1.90 × 10−2 mSv/MBq). 
2.2.3 Catheter Placement 
DCFBC is physiologically excreted through the bladder making visualization of surrounding 
tissue, (primarily the prostate bed in our situation) extremely challenging.  In Arm 2 patients 
specifically, we are looking for possible recurrence within the region that may be very small 
and often overshadowed by the adjacent high urine activity. Mertens et al., described using a 
catheter during FDG imaging that significantly improved visualization and quantification of 
primary bladder cancer [17]. Other groups have also shown better evaluation of gynecologic 
tumors using catheter irrigation [18]. We are hoping to similarly optimize our ability to 
accurately find disease by reducing bladder activity with the catheter. 
2.3 
Rationale 
We propose to further expand upon initial clinical work with 18F DCFBC and evaluate its 
usefulness in three different categories of prostate cancer- localized, metastatic and 
biochemical recurrence. In the case of localized disease 18F DCFBC distribution will be 
compared with endorectal coil multiparametric MRI at 3T.  In the case of potentially recurrent 
or metastatic disease 18F DCFBC will be compared with CT, bone scan and/or Sodium 
Fluoride PET/CT bone scan.  This study should offer insights into how and when 18F DCFBC 
could be used in the clinical setting to direct proper management.  Moreover, by monitoring 
18F DCFBC uptake in metastatic disease over time, one may better understand how useful this 
agent may be in monitoring responses to therapy. 
Amendment C Addendum:  
The agent has shown some preliminary promising results. In Arm 2, we have had patients 
with questionable uptake only near the bladder. We have noted that bladder activity may 
obscure possible prostate bed recurrence, so a recent amendment was approved for urinary 
catheterization with possible bladder irrigation. We have only been able to scan a limited 


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Abbreviated Title: DCFBC in prostate cancer 
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CIP #: 9622 
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number of patients using this technique and have been able to locate areas suspicious for 
recurrence in some. Additional patients will help to determine if the technique is beneficial in 
visualization, potentially improving detection rates for early local recurrence. In Arm 3, we 
have noted a mixed response in tracer uptake for hormone sensitive patients, which 
contradicts what other PSMA research groups are reporting. They assert that uptake is always 
positive in patients on anti-androgen treatment. Our findings could be due to the 
heterogeneous evolution of lesions to castrate resistance, but currently our numbers are small. 
More patients to this arm will allow better characterization of the relationship between 18F 
DCFBC uptake and androgen deprivation therapy. 
Amendment E Addendum:  
To date 31 patients have been scanned on Arm 2.  All are assumed to have recurrent disease 
based on rising PSA.   There have been 20 positive scans (9 in the prostate bed, 8 outside the 
prostate bed (nodes or bone) and 3 both in and out of the prostate bed.  Biopsy is only 
available in 7 but clinical information is supportive (i.e. response to therapy) in 4 more.  Thus, 
the results are still preliminary.   In the range of PSA 0.2-0.5ng/ml the scan is 25% positive,  
0.5-1.0 ng/ml 50%   1.0 to 2.0ng/ml 40% and >2.0ng/ml  85%.  However, the first 10 patients 
were done without irrigation catheters and this undoubtedly explains some of the findings.  
The first expansion request for Arm 2 was to get more patients with bladder irrigation 
catheters after we recognized that bladder-urethra activity was probably hiding some lesions.  
We now have over 20 patients in that category. Having shown some promising results, the 
purpose of this expansion cohort is to better define the sensitivity of DCFBC as a function of 
serum PSA.  This should be a useful metric for comparing DCFBC with the next agent, 
DCFPyl which is reputed to have higher sensitivity.  Thus, the basis of our request is to obtain 
more accurate assessment of the sensitivity of this agent as a function of PSA in patients with 
biochemical recurrence. 
 


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Abbreviated Title: DCFBC in prostate cancer 
Version date: 10/27/2015 
CIP #: 9622 
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3 
PATIENT SELECTION 
3.1 
Eligibility Criteria 
3.1.1 Subject is ≥18 years old  
3.1.2 Platelet count > 50,000/mm3 
3.1.3 Eastern Cooperative Oncology Group (ECOG) Performance score of 0 to 2. 
3.1.4 Ability to provide informed consent.  All subjects must sign an informed consent form 
indicating their understanding of the investigational nature and risks of the study 
before any protocol-related studies are performed. 
3.1.5 Categories 
3.1.5.1 ARM 1 only 
3.1.5.1.1 For patients with presumed localized disease (any T, N0, M0), a multiparametric 
MRI (standard of care at the NIH Clinical Center) must be performed within 4 
months of the 18F-DCFBC  injection with findings suggestive for prostate cancer 
and a prostate lesion at least 6mm or greater. Must have histopathologic 
confirmation of prostate cancer prior to 18F-DCFBC imaging. 
3.1.5.2 ARM 2 only:   
3.1.5.2.1 For patients status post radiation therapy for prostate cancer, any PSA increase 
from post radiation therapy nadir  
OR 
3.1.5.2.2 For patients status post prostatectomy, a PSA >/=0.2 ng/ml 
3.1.5.2.3 Nonspecific or no evidence for disease on standard imaging modality 
3.1.5.3 ARM 3 only: 
3.1.5.3.1 Patients must have identifiable metastatic disease on at least 1 clinically indicated 
imaging modality. If only soft tissue metastasis, one lesion must measure at least 
6mm or greater. Patients must have confirmation of prostate cancer prior to 18F-
DCFBCimaging. 
Note: A patient who is eligible for one arm, subsequently may cross-over into a different arm.  


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Abbreviated Title: DCFBC in prostate cancer 
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CIP #: 9622 
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3.2 
Exclusion Criteria 
3.2.1 Subjects for whom participating would significantly delay the scheduled standard of 
care therapy. 
3.2.2 Subjects with any coexisting medical or psychiatric condition that is likely to interfere 
with study procedures and/or results. 
3.2.3 Subjects with severe claustrophobia unresponsive to oral anxiolytics 
3.2.4 Other medical conditions deemed by the principal investigator (or associates) to make 
the subject unsafe/ineligible for protocol procedures. 
3.2.5 Subjects weighing > 350 lbs. (weight limit for scanner table), or unable to fit within 
the imaging gantry 
3.2.6 Serum creatinine > 2 times the upper limit of normal 
3.2.7 Total bilirubin > 2 times the upper limit of normal 
3.2.8 Liver transaminases (ALT, AST) greater than 3 times the upper limit of normal 
3.3 
Screening Evaluation 
Subjects will be seen by their treating NCI physician and be scheduled to undergo a 
multiparametric 3T MR in the NCI Molecular imaging center as standard of care for Arm 1.  
Confirmation of disease will be made following standard of care biopsy or prostatectomy (not 
part of this protocol) and slides must be reviewed by the Pathology staff at NIH.  For 
presumed biochemical recurrence (Arm 2) or metastatic disease (Arm 3) conventional 
imaging studies and pathology confirmation of the diagnosis of adenocarcinoma of the 
prostate are required. Outside imaging studies can be used to include/exclude metastatic 
disease; however the images must be made available in DICOM format for review by MIP 
staff. 
A screening visit will be performed within 21 days before administration of 18F DCFBC. 
Subjects will be permitted to continue taking any routine or necessary medication. 
All subjects must satisfy all the inclusion criteria and none of the exclusion criteria listed in 
Section 3.1.  Signed, dated and timed informed consent must be obtained from all subjects 
before any study-specific procedures are performed. 
The following data will be collected: 
• Date of birth 
• Weight 
• Height 
• Prior and concurrent medications 
• Medical history and concurrent diseases 
• Results of screening tests: physical examination; vital signs; PSA test 


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Personal data (including contact information) will be collected with the subject’s permission 
and only to the extent that is necessary for the purposes of the study.  Blood samples for 
clinical laboratory tests will be drawn and include a CBC, Acute Care Panel, Hepatic Panel 
and PSA.  Vital signs (BP, HR, RR and Temperature) will be recorded. Temperature will only 
be recorded at baseline, and following the completion of each PET/CT.  A limited physical 
examination will be performed (if not performed within 30 days of 18F DCFBC injection). 
3.4 
Inclusion of Women and Minorities 
Members of all races and ethnic groups are eligible for this trial.  Women are excluded from 
this trial as prostate cancer does not occur in females. 
3.5 
Registration Procedures 
 
 
Authorized staff must register an eligible candidate with NCI Central Registration Office 
(CRO) within 24 hours of signing consent.  A registration Eligibility Checklist from the web 
site (http://home.ccr.cancer.gov/intra/eligibility/welcome.htm) must be completed and faxed 
to 301-480-0757.  Verification of Registration will be forwarded electronically via e-mail to 
the research team.  A recorder is available during non-working hours. 
4 
STUDY IMPLEMENTATION 
4.1 
Study Design 
This is an open-label, 3-armed single-center pilot study.  110 evaluable subjects will be 
enrolled into the study (12 evaluable patients in arm 1; 78 evaluable patients in arm 2, and 20 
evaluable patients in arm 3). An evaluable patient is defined as a patient who completes all 
required study procedures according to the assigned study arm. In order to allow for a small 
number of nonevaluable patients, the accrual ceiling will be set at 125. 
Informed consent will be obtained prior to study enrollment.  All subjects will undergo 18F 
DCFBC injection and PET/CT imaging.  
Patients in Arms 1 and 2 will undergo a single 18F DCFBC PET/CT.  
Patients in Arm 1 will have undergone a standard of care biopsy or clinically indicated 
prostatectomy. Specimens will be whole mounted on glass slides and regions of malignant 
tumor will be marked by the pathologist.  
When possible, uptake of 18F DCFBC depicted on PET/CT in Arms 2 and 3 will be validated 
with biopsy.  
Patients in Arm 2 will be followed for clinical, imaging or pathologic data that may be 
obtained by their medical team within 12 months of imaging to determine if associations with 
18F DCFBC PET/CT can be seen. 


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Subjects in the metastatic disease arm (Arm 3) (as well as individuals who cross over into 
Arm 3) will undergo 2 separate 18F DCFBC PET/CT imaging sessions, one at initial 
enrollment, and a second upon clinical follow-up (4-6 months after baseline 18F DCFBC).  
Patients in Arm 3 will also undergo a whole body Na18F PET/CT scan within 3 weeks of each 
18F DCFBC to assess for potential early bone metastases. Changes in distribution of each 
radiotracer over the 4-6 month period will be compared with clinical data and imaging 
(obtained as standard of care) at that time. Each 18F DCFBC PET/CT will be compared with 
the corresponding Na18F PET/CT scan when obtained.  
4.2 
Stratification Procedures 
4.2.1 Categories 
• ARM 1 
o For patients in the localized disease arm, a multiparametric MRI (standard 
of care at the NIH Clinical Center) with findings suggestive for prostate 
cancer must be performed in the NCI Molecular Imaging Clinic (MIC) 
within 4 months of enrollment and histopathologic confirmation of prostate 
cancer must be done 
• ARM 2 
Patients enrolling into the biochemical relapse arm:  
o For patients status post radiation therapy, any PSA increase from post 
radiation therapy nadir  
OR 
o For patients status post prostatectomy, a PSA >/=0.2 ng/ml 
o Nonspecific or no evidence for disease on standard imaging modality 
• ARM 3 
o Patients in the metastatic monitoring arm must have identifiable metastatic 
disease on at least 1 imaging modality.   
4.3 
Drug Administration 
4.3.1 
18F DCFBC  
See Section 7.1.5. 
4.3.2 
18F NaF Injection 
See section 7.2.4 
4.4 
18F DCFBC PET/CT Imaging  
All images will have personal subject identification removed and will be assigned unique 
subject identification. 
Patients will be instructed to maintain good hydration for the 24 hours prior to the 18F DCFBC 
PET/CT (recommended 1-2 liters of fluid, unless medically contraindicated).   


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Patients will report to the NCI Molecular Imaging Clinic (MIC) on the day of their 18F 
DCFBC PET/CT imaging sessions and peripheral venous access will be obtained.  The patient 
will be encouraged to void prior to positioning in the PET/CT scanner.    
Patency of the venous access will be demonstrated with a saline flush and the patient will then 
receive 8 mCi of 18F DCFBC as an IV bolus.  
Dynamic PET/CT imaging of a single bed position (including the prostate bed) will be 
performed for 45-min for patients in Arm 1 and 2 then, at 60 minutes post injection of 18F 
DCFBC. A static whole body PET/CT will be performed then repeated again at 2hrs post 
injection. Only a single injection of 18F DCFBC is required.  The initial 45 minutes dynamic 
regional scan will be used to determine the kinetics of 18F DCFBC in the tumor as compared 
with normal prostate and other background. 
Patients in Arm 3 will only have static whole body PET/CTs performed at 60 minutes post 
injection and again at 2 hrs post injection. As previous studies have suggested, increased T:B 
uptake is seen at 2 hours compared with 1 hour after radiotracer injection. After 5 patients are 
imaged in each arm, an interim analysis will be done to determine the utility of imaging at 2 
hrs.  
Patients in Arm 2 who have had a prostatectomy may have a 2 or 3 lumen urinary catheter 
inserted to improve visualization of the bladder and adjacent anatomy during imaging. The 
urinary catheter is inserted prior to injection and is removed once all scans are completed. The 
3 lumen catheter will be used to irrigate and empty the bladder during the scan. One lumen is 
used to inflate the balloon to secure the catheter in the bladder, the second lumen allows for 
continuous drainage of urine from the bladder during imaging and the third lumen allows for 
inflow of fluids.  The catheter will be attached to an irrigation system that will allow for better 
visualization of the bladder and adjacent anatomy. 
After the patient is injected with the radiotracer, the bladder will be filled with up to 500cc of 
saline via the third inflow arm of the urinary catheter.  The outflow arm is attached to the 
drainage bag which has a clamp.  The clamp on the drainage bag will closed to allow for 
collection of the urine in the bladder.  Approximately ten minutes before the patient is 
scanned the clamp on the drainage bag will be opened to allow for drainage of the bladder.  
The clamp will remain open during the imaging session to allow for continuous drainage of 
the bladder.   This procedure will be repeated prior to the 2 hrs post-injection scan.  Once all 
scans are completed the catheter will be removed.   
A 2 lumen catheter will be used in lieu of the 3 lumen catheter to keep the bladder empty, if 
the patient cannot tolerate the insertion of a 3 lumen catheter. 
If a patient is not able to tolerate catheter placement, they will be asked to empty their bladder 
frequently during the PET uptake phase and immediately prior to whole body PET/CT 
imaging. 


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A corresponding low dose CT scan for attenuation correction and co-registration purposes 
will be performed prior to each PET image (i.e. 1-single bed position including the prostate 
bed, and 2 whole body (1 each for the 1-hr and 2 hr images). All whole body 18F DCFBC 
PET/CT images will be obtained from the top of the skull down to the thighs. 
4.4.1 Summary of scanning procedure: 
1. IV placement 
2. If not previously drawn within 30 days of 18F DCFBC, blood will be drawn for PSA 
measurement 
3. Subject asked to void (Arm 2 patients will receive a urinary catheter which will be 
removed once all imaging is completed). 
4. Administration of 18F DCFBC; begin AE monitoring 
5. Initial positioning in the scanner and single bed position low dose transmission CT 
6. For Arm 1 and Arm 2 patients: 45-minute dynamic imaging of the pelvis  
7. Subject asked to void 
8. 1 hour following 18F DCFBC injection, whole body PET/CT imaging will be 
performed (~45 minutes in duration) 
9. Another whole body PET/CT scan will be performed (~45 minutes) at 2 hours post-
injection of 18F DCFBC   
10. Follow-up AE query ~1-3 days post-injection 
4.5 
18F NaF PET/CT Imaging 
18F NaF PET/CT Imaging (only in ARM 3 subjects, may be performed as clinical standard of 
care in this or other arms) 
Patients undergoing 18F NaF PET/CT Imaging at NCI/MIC are instructed to maintain good 
hydration for the 24 hours prior to the 18F NaF PET/CT (recommended 1-2 liters of fluid, 
unless medically contraindicated).  Patients will report to the NCI MIC on the day of their 18F 
NaF PET/CT imaging sessions and peripheral venous access will be obtained (most 
commonly via IV in the antecubital fossa).  The patient will be encouraged to void prior to 
positioning in the PET/CT scanner.  A low dose non-diagnostic transmission CT will be 
performed. Patency of the venous access will be demonstrated with a saline flush and the 
patient will then receive 3mCi of 18F NaF IV bolus. 
4.5.1 Whole body PET/CT 
A whole body PET/CT will be performed beginning 1 hour post 18F NaF injection.   
Good hydration is recommended in order to reduce excessive radiation exposure.  The patient 
should void one-half hour after the administration of 18F NaF Injection and as frequently 
thereafter as possible. 


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4.6 
Additional Imaging 
1. For subjects with known metastatic disease (Arm 3), additional Na18F PET/CT and 18F 
DCFBC PET/CT will be performed, within 3 weeks of each other and within 4-6 months 
following the initial scans. 
2. Additional PET/MR imaging may be done if scheduling allows, and the subject does not 
have any MR incompatible conditions or implants) immediately after F18 DCFBC 
PET/CT  in all arms to explore visibility of anatomic correlates to tracer uptake between the 
two modalities. No additional radiation risk is involved.  
Patients who will undergo additional PET/MR will first complete the PET/CT portion in the 
Molecular Imaging Clinic (MIC). They will then be escorted to the Clinical Center Radiology 
Department for PET/MR imaging. Arm 2 patients with urinary catheters will have them 
removed prior to leaving MIC. 
MRI image acquisition will follow with sequences acquired with standard MRI imaging in 
order to spatially correlate findings, which may include T2W, diffusion, and MRSI. 
Simultaneous PET emission data will be acquired with MRI images. This portion of the study 
will last approximately 1 hour. MR contrast will not be used to this portion of the visit, and no 
additional radiotracer will be injected. 
4.7 
Pathology 
4.7.1 Surgical Pathology (Standard of care, for ARM 1 only) 
Specimens will undergo standard preparation and sectioning in the Department of Surgical 
Pathology for pathological diagnosis.  Additional sectioning and IHC staining may also be 
conducted by an approved outside pathology laboratory. Prostatectomy specimens will be 
processed by patient specific MRI based specimen molds to provide geometric and spatial 
alignment between MRI, PET and histopathology. The specimen results will be correlated 
with 18F DCFBC PET/CT results and MRI imaging results. 
4.8 
Biopsy 
Biopsy of abnormal sites of uptake will not be required by this protocol; however if a 
suspicious focus of uptake is identified, this information will be communicated to the 
referring physician, who may choose to evaluate the site further with biopsy or clinical 
follow-up. In such a case any follow-up information obtained (including pathology) will be 
collected as clinically needed. 
4.9 
Correlative Studies 
4.9.1 Imaging Correlation 
A volume of interest (VOI) will be drawn over the target lesion on the PET/CT and PET/MRI 
(if PET /MRI is obtained) images for each subject and Standard Uptake Values (SUVs) will 


CC Protocol Number: 
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Abbreviated Title: DCFBC in prostate cancer 
Version date: 10/27/2015 
CIP #: 9622 
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be recorded. Focal areas of abnormal uptake will be compared with any abnormalities on 
standard of care imaging.  
4.9.2 Pathologic and Imaging Correlation 
NIH Clinical Center prostatectomy or standard of care biopsy is planned for subjects enrolled 
in ARM 1 (localized disease). The specimen results will be correlated with 18F DCFBC 
PET/CT and MRI results. 
Following radical prostatectomy, surgical specimens will undergo standard preparation and 
sectioning in the Department of Surgical Pathology for pathological diagnosis.  Urologists 
from the UOB at the NIH Clinical Center have extensive experience with laparoscopic 
prostatectomy.  The surgical specimen obtained with the laparoscopic procedure is preserved 
at least as intact as in open laparotomy procedures.  To date, the UOB has performed over 250 
MRI/pathology correlations after laparoscopic prostatectomies.  
At resection, the specimen is painted with three different colored inks (anterior right with 
blue, anterior left with red and urethral side with yellow) for correct orientation, and the gland 
is left to dry for 1-2 minutes.  The gland is divided into two equal parts in the axial plane; 
from one of these parts, a rectangular sample of 2x1x0.2 cm is taken for DNA analysis – it is 
understood that this sample may contain cancer tissue and may not be reported. The DNA 
analysis is for research interest of the NCI and is not a component of this protocol.  The two 
cut parts are re-glued for fixation.  Fresh prostate gland is hard to hold and cut, so slicing after 
fixation is better and easier.  The glued and combined gland is kept in formalin for 24 to 
48 hours at room temperature for fixation.  After fixation, the seminal vesicles are removed 
and then the gland is sliced via a custom-made mold based on the 3D imaging information 
from high resolution T2W MR images.  The molds are equipped with slots spaced 6 mm apart.  
The gland only shrinks by approximately 3% after the first fixation and prior to slicing.  A 
single-blade steel knife is used for one prostate.  In this manner, attempts will be made to cut 
the specimens in the same plane as the imaging was performed.  The sliced gland is kept 
within formalin for as long as a week at room temperature.  The tissue is processed into 
paraffin blocks and sectioned by standard methods.  The gland shrinks by 10-15% after all of 
these procedures. 
Slide specimens will be stained for morphology and regions with malignant tumor, non-
malignant pathologies, and normal tissue will be marked by the pathologist. The resultant 
pathologic specimen is cut transversely using the same alignment as the T2W MR images.  
Thus, the MRI and PET/CT scans are approximately aligned with the prostate specimens. 
Tumor extent, Gleason Score and presence of BPH, and inflammation on tissue sections will 
be evaluated and correlated with uptake of 18F DCFBC. 


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4.9.3 PET: MR comparison (Arm 1 or other MR available) 
The distribution of uptake of 18F DCFBC depicted by PET/CT will be compared with tumor 
indicators observed on the MR image data (T2W MRI, DCE MRI, MR DWI, and MRSI) on a 
per-subject and per-lesion basis. 
In case the new imaging agent shows an unexpected finding, this may be correlated with 
conventional imaging.   
4.10 Off-Study Criteria 
In cases where a subject withdraws or is withdrawn from the study after administration of 18F 
DCFBC and before surgery or biopsy is performed, a replacement subject will be enrolled.  
Should a subject withdraw after administration of 18F DCFBC, or should the investigators 
decide to withdraw the subject, all efforts will be made to complete and report the protocol-
stipulated observations up to the time of withdrawal as thoroughly as possible.  A final 
evaluation at the time of the subject’s withdrawal should be made and an explanation given of 
why the subject is withdrawing or being withdrawn from the study.  The reason and date and 
time of withdrawal must be recorded.  If the reason for withdrawal is a clinical AE, 
monitoring will continue until the outcome or stabilization is established. 
Patients will be taken off treatment upon completion of all study procedures.  The patients 
will be taken off study one year after the follow-up period.  During this one year time period, 
the patient’s PSA levels and prostate cancer related medical history, biopsy results, imaging 
studies and will be collected. 
 
4.10.1 Criteria for Removal from Protocol 
• Investigators have the right to withdraw subjects from the study in the event of illness, 
AEs, or other reasons concerning the health or well-being of the subject, or in the case 
of lack of co-operation. 
• Subject completes a one year follow-up period upon completion of all study 
procedures 
• Subjects can be taken off study at the discretion of the Investigator. 
• Patient requests to be taken off study 
• Patient non-compliance with protocol guidelines 
• A serious or intolerable adverse event related to the study drug occurs 
• Patient may not be taken off study until intolerable adverse event has stabilized or 
resolved. 
4.10.2 Off-Study Procedure 
Authorized staff must notify Central Registration Office (CRO) when a subject is taken off-
study.  An off-study form from the web site 


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(http://home.ccr.cancer.gov/intra/eligibility/welcome.htm) main page must be completed and 
faxed to 301-480-0757. 
4.11 Follow-up  
All subjects will be contacted by phone ~1-3 days post injection and will be asked a non-
leading question to determine whether any new AEs have occurred and to follow up on any 
ongoing AEs since completion of PET imaging. If the patient is being evaluated in person 24 
hours post-injection then a phone call will not be necessary. 
Within 4-6 months following PET imaging the clinically indicated surgery or biopsy 
procedure will be performed. 
5 
Dose Modifications 
Due to potential unpredictable delays and the short half-life of 18F, the total dose of 18F 
DCFBC administered may be reduced at the discretion of the principal investigator or her 
designee.   
6 
ADVERSE EVENTS:  LIST AND REPORTING REQUIREMENTS  
Adverse event (AE) monitoring and reporting is a routine part of every clinical trial.  The 
following list of AEs (Section 6.1) and the characteristics of an observed AE (Section 6.1.1.1) 
will determine whether the event requires expedited reporting (via CTEP-AERS) in addition 
to routine reporting. 
6.1 
Comprehensive Adverse Events and Potential Risks List (CAEPR) 
The Comprehensive Adverse Event and Potential Risks list (CAEPR) provides a single list of 
reported and/or potential adverse events (AE) associated with an agent using a uniform 
presentation of events by body system.  In addition to the comprehensive list, a subset of AEs, 
the Specific Protocol Exceptions to Expedited Reporting (SPEER), appears in a separate 
column and is identified with bold and italicized text.  The SPEER is a list of events that are 
protocol-specific exceptions to expedited reporting to NCI via CTEP-AERS (except as noted 
below).  Refer to the 'CTEP, NCI Guidelines: Adverse Event Reporting Requirements' 
http://ctep.cancer.gov/protocolDevelopment/adverse_effects.htm for further clarification.  
NOTE:  The highest grade currently reported is noted in parentheses next to the AE in 
the SPEER.  Report ONLY AEs higher than this grade expeditiously via CTEP-
AERS.  If this CAEPR is part of a combination protocol using multiple investigational 
agents and has an AE listed on different SPEERs, use the lower of the grades to 
determine if expedited reporting is required. 
Please note that a CAEPR has not been developed for 18F DCFBC to-date.  However, once 
available, the protocol will be updated to include this information.  
6.1.1.1 Adverse Event Characteristics  
• CTCAE term (AE description) and grade:  The descriptions and grading scales 
found in the revised NCI Common Terminology Criteria for Adverse Events 
(CTCAE) version 4.0 will be utilized for AE reporting.  All appropriate treatment 
areas should have access to a copy of the CTCAE version 4.0.  A copy of the CTCAE 


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version 4.0 can be downloaded from the CTEP web site 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm. 
 
• For expedited reporting purposes only:   
- 
AEs for the agent that are bold and italicized in the CAEPR should be reported 
through CTEP-AERS only if the grade is above the grade provided in the SPEER. 
 
• Attribution of the AE: 
- 
Definite – The AE is clearly related to the study treatment. 
- 
Probable – The AE is likely related to the study treatment. 
- 
Possible – The AE may be related to the study treatment. 
- 
Unlikely – The AE is doubtfully related to the study treatment. 
- 
Unrelated – The AE is clearly NOT related to the study treatment. 
6.2 
Expedited Adverse Event Reporting to CTEP 
Expedited AE reporting for this study must use  
 CTEP Adverse Event Reporting System (CTEP-AERS), accessed via the CTEP Web site 
(http://ctep.cancer.gov).  The reporting procedures to be followed are presented in the “NCI 
Guidelines for Investigators: Adverse Event Reporting Requirements for DCTD (CTEP and 
CIP) and DCP INDs and IDEs” which can be downloaded from the CTEP Web site 
(http://ctep.cancer.gov).  These requirements are briefly outlined in the tables below (Section 
6.2.1). 
In the rare occurrence when Internet connectivity is lost, a 24-hour notification is to be made 
to CTEP by telephone at 301-897-7497.  Once Internet connectivity is restored, the 24-hour 
notification phoned in must be entered electronically into CTEP-AERS by the original 
submitter at the site. 
6.2.1 Expedited Reporting Guidelines 
Use the NCI protocol number and the protocol-specific patient ID assigned during trial 
registration on all reports. 
Note:  A death on study requires both routine and expedited reporting regardless of 
causality, unless as noted below.  Attribution to treatment or other cause must be 
provided. 
Death due to progressive disease should be reported as Grade 5 “Neoplasms benign, 
malignant and unspecified (incl cysts and polyps) - Other (Progressive Disease)” under 
the system organ class (SOC) of the same name.  Evidence that the death was a manifestation 
of underlying disease (e.g., radiological changes suggesting tumor growth or progression: 
clinical deterioration associated with a disease process) should be submitted.  
Phase 0 Studies:  Expedited Reporting Requirements for Adverse Events that Occur on 
Studies under an IND/IDE within 30 Days of the Last Administration of the 
Investigational Agent/Intervention1, 2 
FDA REPORTING REQUIREMENTS FOR SERIOUS ADVERSE EVENTS (21 CFR Part 312) 
NOTE:  Investigators MUST immediately report to the sponsor (NCI) ANY Serious Adverse Events, whether or not 
they are considered related to the investigational agent(s)/intervention (21 CFR 312.64) 


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An adverse event is considered serious if it results in ANY of the following outcomes:   
1) 
Death 
2) 
A life-threatening adverse event  
3) 
An adverse event results in inpatient hospitalization or prolongation of existing hospitalization for ≥ 24 
hours  
4) 
A persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions  
5) 
A congenital anomaly/birth defect.  
6) 
Important Medical Events (IME) that may not result in death, be life threatening, or require hospitalization 
may be considered serious when, based upon medical judgment, they may jeopardize the patient or 
subject and may require medical or surgical intervention to prevent one of the outcomes listed in this 
definition (FDA, 21 CFR 312.32; ICH E2A and ICH E6). 
 
ALL SERIOUS adverse events that meet the above criteria MUST be immediately reported to the NCI via CTEP-
AERS within the timeframes detailed in the table below. 
Grade 1 and 2 Timeframes 
Grade 3-5 Timeframes 
10 Calendar Days 
24-Hour 5 Calendar Days 
Expedited AE reporting timelines are defined as: 
o 
“24-Hour; 5 Calendar Days” - The AE must initially be reported via CTEP-AERS within 24 hours of learning 
of the AE, followed by a complete expedited report within 5 calendar days of the initial 24-hour report. 
o 
“10 Calendar Days” - A complete expedited report on the AE must be submitted within 10 calendar days of 
learning of the AE. 
1Serious adverse events that occur more than 30 days after the last administration of investigational 
agent/intervention require reporting as follows:   
Expedited 24-hour notification followed by complete report within 5 calendar days for ALL Grade 4 and 5 AEs and 
Grade 3 AEs with at least a possible attribution.   
2For studies using PET or SPECT IND agents, the AE reporting period is limited to 10 radioactive half-lives, 
rounded UP to the nearest whole day, after the agent/intervention was last administered.  Footnote “1” above 
applies after this reporting period. 
Effective Date:  May 5, 2011 
6.3 
Routine Adverse Event Reporting to CTEP 
All Adverse Events must be reported in routine study data submissions.  AEs reported 
through CTEP-AERS must also be reported in routine study data submissions. 
6.4 
Secondary Malignancy 
A secondary malignancy is a cancer caused by treatment for a previous malignancy (e.g., 
treatment with investigational agent/intervention, radiation or chemotherapy). A secondary 
malignancy is not considered a metastasis of the initial neoplasm.  
CTEP requires all secondary malignancies that occur following treatment with an agent under 
an NCI IND/IDE be reported via CTEP-AERS. Three options are available to describe the 
event:  
• Leukemia secondary to oncology chemotherapy (e.g., acute myelocytic leukemia 
[AML])  
• Myelodysplastic syndrome (MDS)  
• Treatment-related secondary malignancy  
Any malignancy possibly related to cancer treatment (including AML/MDS) should also be 
reported via the routine reporting mechanisms outlined in each protocol.  


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6.5 
Second Malignancy 
A second malignancy is one unrelated to the treatment of a prior malignancy (and is NOT a 
metastasis from the initial malignancy).  Second malignancies require ONLY routine 
reporting via CDUS unless otherwise specified.  
7 
PHARMACEUTICAL INFORMATION 
7.1 
18F DCFBC (CIP # 122053) 
7.1.1 Classification:  
Radiopharmaceutical for imaging 
7.1.2 Chemical Name:  
N-[N-[(S)-1,3-Dicarboxypropyl]carbamoyl]-4-[18F]fluorobenzyl-L-cysteine 
7.1.3 C.A.S Number:  
564482-79-7 
7.1.4 How supplied:   
18F DCFBC is a sterile, IV injectable solution with a volume of ≤ 15 mL containing normal 
saline: 6.7% ethanol (V:V) 
7.1.5 Route of Administration:  
Subjects will receive 18F DCFBC under the direct supervision of study personnel.  Each 
subject will receive a single i.v. dose of 18F DCFBC by bolus injection at a rate of 
approximately 1 ml/3-5 sec.  The maximum amount of injected active drug will be 50 µg. The 
injection will be followed by a 10-ml saline flush (sodium chloride iv infusion 0.9% w/v) over 
~10sec. 
The target administered activity will be 8 mCi; dose variations will be in accordance with the 
Nuclear Regulatory Commission (NRC) standard dose variation (i.e. 20%) permitted for 
diagnostic clinical studies. The administered activity has been based upon the results of 
dosimetry analysis on data from 18F DCFBC prior pre-clinical and human studies.   
The administration site should be evaluated just before, during and after injection, to assess 
for extravasation and/or for the presence of signs of local irritation. 
A member of the Molecular Imaging Program clinical team will be in attendance during the 
injection.  In the event of an emergency, such as an allergic reaction, immediate treatment will 
be initiated using emergency medication available in the Molecular Imaging Clinic.  If the 
subject requires admission due to the severity of the reaction, the subject will be admitted to 
the appropriate service for observation as the clinical situation dictates. 
Any administration complication of the drug (e.g., overdose, observable extravasation, 
medication error) is a protocol related event and will be reported. 
 


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Due to potential unpredictable delays and the short half-life of 18F, the total dose of 18F 
DCFBC administered may be reduced at the discretion of the principal investigator or her 
designee. 
7.1.6 Adverse Events and Potential Risks: 
A list of the adverse events and potential risks associated with 18F DCFBC can be found in 
Section 2.2.1.2. 
7.1.7 Production of the Radiopharmaceutical: 
The 18F DCFBC used in this study is prepared locally by the Leidos Biomedical Research, 
Inc. radiopharmacy, Frederick, MD.  
Manufacture of 18F DCFBC drug substance and formulation, sterilization and filling of18F 
DCFBC Injection drug product, is a continuous process whereby the drug substance is never 
isolated or held. Immediately upon completion of the radiosynthesis reaction that forms18F 
DCFBC drug substance, the reaction mixture is purified by high performance liquid 
chromatography and formulated in a solution of Sodium Chloride Injection (0.9%) containing 
ethanol. A sample is removed for analytical testing under septic conditions for chemical and 
radiochemical quality control analysis, and bacterial endotoxin and sterility testing. This 
completes the manufacture of 18F DCFBC Injection. The batch consists of about 15 mL of 
formulated drug product contained in a single 20 mL vial. It is held in quarantine pending 
completion of required quality control testing and release. 
7.1.8 Agent Ordering: 
18F DCFBC will be ordered from the Leidos Biomedical Research, Inc. Radiopharmacy using 
the form supplied in Appendix B; orders should be placed 5 business days prior to the 
scheduled 18F DCFBC scan date and time. 
George Afari, PharmD, BCNP 
Clinical Radiopharmacist 
Applied/Developmental Research Directorate,  
Leidos Biomedical Research, Inc. 
National Cancer Institute-Frederick 
Phone: 301 846 7391 
Fax: 301 846 5935 
E-mail: george.afari@nih.gov  
7.1.9 Agent Returns: 
If for any reason the study imaging is unable to be completed, sites will allow the 
radioactivity of the 18F DCFBC solution to decay and then discard it appropriately per site’s 
policies and procedures, making a record of the event as required. A copy of the policy should 
be available upon request. 
7.1.10 Source 
18F DCFBC will be prepared and handled by Leidos Biomedical Research, Inc., 
Radiopharmacy according to the chemistry and manufacturing described in the IND. A 
delivery sheet/protocol will be provided with each delivery of 18F DCFBC which will contain 


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the batch number, time of preparation, radioactive concentration (mCi/ mL) at a stated time, 
and shelf-life information. The delivery sheet/protocol will include the expiration date and 
time (hh:mm), based on the chemical stability of the synthesized compound. 
Before administration, the suitability of each preparation will be assessed by a number of QC 
tests ran by the manufacturer, which may include radioactivity content by well-counting, 
radiochemical purity by thin-layer chromatography, chemical content, and pH measurement, 
according to approved methods provided by in the IND. A document attesting to the passing 
of these quality control (QC) processes will be provided to the Molecular Imaging Clinic. 
Dr. Liza Lindenberg or an appropriate designee will review the documentation provided to 
ensure that the product quality meets the criteria for clinical use defined within the IND, and 
to certify (verbally, in writing or via email) that 18F DCFBC is released for clinical use. The 
medically responsible person at the PET imaging site will ensure that the correct dose is 
present in the injection syringe and that the product is used within the stability period of time 
stated on the delivery sheet/protocol prior to injection. A lower amount of radioactivity 
(potentially due to an unpredictable delay in delivery or injection time) may be administered 
at the discretion of Dr. Liza Lindenberg or an appropriate designee, and will be documented. 
7.1.11 Agent Inventory Records –  
The CIP regulatory staff will inform the commercial radiopharmac(y/ies) that your NCI 
protocol is authorized to use the IND agent under NCI’s IND.  The IND agent can then be 
purchased from a NCI CIP AUTHORIZED commercial vendor under the NCI IND.   The 
vendor must be specifically authorized within the NCI IND.  The investigator or appropriate 
investigator-designee will order subject doses of the IND agent for this specific trial.  The 
investigational radiopharmaceutical will be shipped to the site by the day the participant is to 
be injected, taking into account varying radioactive half-lives for different radioactive 
imaging agents.   
7.1.12 Stability and Storage 
The in-use shelf-life of 18F DCFBC will be specified on the label.  Although from a chemical 
perspective, the product remains stable beyond 6 hours, due to the short 109.8-minute half-life 
of 18F, the low level of activity present after 6 hours renders it unsuitable for positron imaging 
tomography studies.  18F DCFBC is stored in the original container at 4 °C under inert 
atmosphere. 
7.1.13 Supply and Packaging 
18F DCFBC for each study patient will be received in individual patient doses from the 
manufacturer. Containers that are radioactive or contain radioactive products will be disposed 
of per NIH Radiation Safety Guidelines. 


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7.2 
18F NaF Source:  
18F NaF will be obtained from Cardinal Health, Beltsville, MD, IBA, Sterling VA, PETNET 
Solutions Inc., Philadelphia, PA, or other commercial vendor according to the DMFs filed 
with the FDA respectively.  
7.2.1 Toxicity   
Fluoride is a normal body constituent.  The amount of fluoride ions in 18F NaF Injection at the 
indicated dose is expected to have minimal effect on normal human physiology.  When 18F 
NaF Injection was approved for marketing in 1972, no adverse reactions were noted in over 
400 patient studies reported in the medical literature [16].  In a 1999 review of the published 
literature, publicly available reference sources and adverse drug reaction reporting systems 
indicated that no adverse reactions have been reported for 18F NaF Injection[16].   
The safety and effectiveness of 18F NaF Injection has not been established in pediatric 
patients, and prudence suggests limiting exposure in growing children; carefully selected 
pediatric use has been reported. 
7.2.2 Formulation and preparation 
Supplied as a unit dose, 300-450 MBq (8.0 to 12.0 mCi) or as a multi-dose vial containing 
370–14,800 MBq/mL (10–400 mCi/mL) of no-carrier-added sodium [18F] fluoride at the end 
of synthesis (EOS) reference time in aqueous 0.9% sodium chloride solution.  If supplied as a 
multi-dose vial, a unit dose (3-5 mCi) will be aseptically drawn from the multi-dose container 
for intravenous injection.  
7.2.3 Stability and storage 
Store at 25°C (77°F); excursions permitted to 15–30°C (59–86°F).  Use the solution within 12 
hours of the EOS calibration time printed on the label. 
7.2.4 Administration procedure 
IV bolus followed by saline flush. 18F NaF Injection preparations containing particulate matter 
or discoloration will not be administered. To maintain sterility, aseptic technique will be used 
during all operations involved in the manipulation and administration of 18F NaF Injection.  
The patient should be instructed to ingest copious amounts of fluid 1-2 hours prior and 
following 18F NaF PET/CT imaging. The patient should void just prior to imaging and 
maintain hydration and as frequently thereafter as possible.  
8 
Study Calendar 
All measurements obtained during the course of the study are summarized in the Study 
Calendar 8.1.1. 
The timing of study events in the following descriptions is relative to the administration of 18F 
DCFBC.  


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8.1.1 Study Calendar 
 
Screening a 
PET/CT Imaging a, b 
Post- PET Imaging 
d 
Up to -30 days 
(screening) 
F-18 DFBC I.V. 
injection 
+15 min  
+30 min 
+1 hours b 
+2 hours 
+1-3 days  post  dose 
administration  
Arm 1 patients: 
Within 4-6 months 
following PET/CT 
imaging
Informed consent 
• 
 
 
 
 
 
 
 
Study entry criteria 
• 
 
 
 
 
 
 
 
Demographic information 
• 
 
 
 
 
 
 
 
Medical history and concurrent diseases 
• 
 
 
 
 
 
 
 
Prior/concomitant medication 
• 
 
 
 
 
 
 
 
Limited physical examination c 
• 
 
 
 
 
 
 
 
Injection site monitoring 
 
• 
• 
• 
• 
 
 
 
Vital signs 
• 
 
• 
• 
• 
• 
 
 
Blood samples for PSA 
• 
 
 
 
 
 
 
 


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Screening a 
PET/CT Imaging a, b 
Post- PET Imaging 
d 
Up to -30 days 
(screening) 
F-18 DFBC I.V. 
injection 
+15 min  
+30 min 
+1 hours b 
+2 hours 
+1-3 days  post  dose 
administration  
Arm 1 patients: 
Within 4-6 months 
following PET/CT 
imaging
AE Monitoring/Query  
 
• 
• 
• 
• 
• 
• 
 
18F DCFBC administration  
 
• 
 
 
 
 
 
 
Tissue Sample e 
 
 
 
 
 
 
 
•  
PET/CT Imaging 
 
 
 
 
• 
• 
 
 
8.1.2 Procedures conducted during Follow-up  
Occurs 4-6 months after initial scans 
 
Follow-Up Imaging f 
Vital signs 
• 
AE Monitoring/Query  
• 
18F DCFBC administration  
• 


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Follow-Up Imaging f 
PET/CT Imaging 
• 
NOTE:  Shaded areas depict continuous measurement or monitoring. 
a. Timing of events is relative to administration of 18F DCFBC. 
b. At the investigator's discretion, subjects with safety concerns noted during the post-injection period may remain at the site or be 
asked to return to the site to undergo further safety assessments at the1-3 days post-injection time point.  
c. If not performed within 30 days of 18F DCFBC injection on H&P or SOAP note 
d. All subjects will be contacted by phone at ~1-3 days post-injection and will be asked non-leading questions (i.e., such as “How 
are you doing”, “Are you having any problems?”) to determine whether any new AEs have occurred and to follow up on any 
ongoing AEs. 
e. Pertains to subjects in ARM 1. 
f. Performed in subjects with known metastasis (ARM 3). Subjects in this arm will also receive an 18F NaF PET/CT Imaging. Each 
set of Na18F PET/CT and 18F DCFBC PET/CT will be performed within 3 weeks of each other. 
 


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8.1.3 Study Periods 
8.1.3.1 Screening Period 
Refer to section 3.3 
8.1.3.2 
18F DCFBC PET/CT Imaging Period 
Refer to section 8.1.1 
Monitoring of AEs will start when 18F DCFBC is administered.  Study personnel will remain 
vigilant for the occurrence of AEs, particularly those that may be life-threatening.  Personnel 
trained in the acute management of anaphylaxis and other emergencies and who have access to 
appropriate clinical supplies will be immediately available for no less than 30 minutes to 
observe for possible anaphylactic reactions after dosing.  Treatment of serious AEs should be 
primarily supportive of vital functions.  The subjects will be closely observed and questioned 
for any kind of AE during the study procedures with non-leading questioning (e.g., “How do 
you feel?”).  The subjects will be instructed to immediately report any symptoms and signs to 
the study staff (i.e., between formal observations). 
Vital signs will be taken prior to injection, 15 and 30 minutes after injection and following 
completion of each PET/CT scan. 
At the end of the last PET/CT scan, the following safety assessments will be conducted: 
injection site monitoring, vital signs, and AE query. At the investigator's discretion, subjects 
with safety concerns noted during the post-injection period may remain at the site or be asked 
to return to the site to undergo further safety assessments at the 1-3 day follow-up time point. 
8.1.3.3 Vital Signs 
Vital signs will be measured at various pre- and post-injection time points described in the 
Study Calendar.  Vital sign parameters include measurements of systolic and diastolic BP, 
heart rate and respiratory rate. 
The interpretation and follow-up of abnormal vital signs results should be conducted on a case 
by case basis in conjunction with the individual clinical situation. 
8.1.3.4 Physical Examination 
Qualified study personnel will conduct all physical examinations. Limited physical 
examination will be performed as described in the Study Calendar. 
In the event that new and worsening abnormal physical examination findings are encountered 
during the study, these terms are defined as follows: a new abnormal physical examination 
finding is defined as one that occurs when a subject’s normal baseline physical examination 
becomes abnormal post-baseline, based on clinical grounds.  A worsening abnormal physical 


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examination finding is defined as one that occurs when a subject's abnormal baseline physical 
examination becomes worse post-baseline, also based on clinical grounds.  In both cases, 
observations will be collected as AEs. 
8.1.3.5 Injection Site Monitoring 
Injection site monitoring will be performed prior to administration of the imaging agent and at 
various time points post-injection described in the Study Calendar.  Any abnormal findings 
during this period will be recorded as an AE on the research record.  Abnormal injection site 
findings include, but are not limited to, radiopharmaceutical extravasation, bleeding, 
hematoma, redness and infection. 
Any abnormal finding that is new or represents a worsening from baseline is an AE.  Once AE 
notification is decided upon, investigators are required to follow the procedure described for 
AE notification and document the abnormal finding in the subject’s research record. 
8.1.3.6 Pre-Administration Events 
The presence of any pre-administration event (baseline signs and symptoms present just before 
18F DCFBC administration) will be recorded in C3D.  
The following information will also be recorded: 
• The date and time of evaluation 
• The onset time 
• The resolution time or duration 
• Action taken 
• Status of symptom 
• Intensity 
8.2 
Surgical Guidelines 
No surgical procedures will be dictated by this protocol. However, if any such procedures do 
occur, the results will be documented. 
In the event that the 18F DCFBC PET/CT scan demonstrates an unexpected finding, it may be 
correlated with conventional imaging.  The referring physician will use best clinical judgment 
in determining the risks and benefits of changing the surgical procedure in light of the new 
findings based on the correlation with conventional testing. 
8.3 
Radiation Therapy Guidelines 
Any sites of radiation therapy must be documented (site, date began, duration, dose, and 
technique). Radiation therapy will not be dictated by this protocol. 


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9 
DATA REPORTING / REGULATORY REQUIREMENTS 
Adverse event lists, guidelines, and instructions for AE reporting can be found in Section 6 
(Adverse Events: List and Reporting Requirements). 
9.1 
Data Reporting 
9.1.1 Method 
This study will be monitored by the Clinical Data Update System (CDUS) version 3.0. 
Cumulative CDUS data will be submitted quarterly to CTEP by electronic means.  Reports are 
due January 31, April 30, July 31 and October 31.  Instructions for submitting data using the 
CDUS can be found on the CTEP web site (http://ctep.cancer.gov/reporting/cdus.html). 
Note:  All adverse events that have occurred on the study, including those reported through 
CTEP-AERS, must be reported via the monitoring method identified above. 
9.1.2 Responsibility for Data Submission 
N/A 
10 Cooperative Research and Development Agreement (CRADA) / Clinical Trials 
Agreement (CTA) 
N/A 
11 CONCOMITANT MEDICATION/MEASURES 
In the event that a subject has a reaction (allergic) to the radiotracer, all appropriate medical 
measures will be taken immediately.  In rare instances, this may entail admission to the 
hospital for observation. 
12 DATA COLLECTION AND EVALUATION 
12.1 Data Collection 
12.1.1 Clinical Data 
All data will be kept secure.  Personal identifiers will not be used when collecting and storing 
data. An enrollment log will be maintained in the regulatory binder/file which is the only 
location of personal identifiers with unique subject identification number. 
Clinical data including summary and demographic data will be collected and entered into NCI 
CCR Database, C3D.  Adverse events occurring during any scanning session will be recorded.  
Adverse events which are designated possibly, probably or definitely related to 18F DCFBC 
will also be recorded. 
Imaging data will include storage of the reconstructed images and image derived parameters on 
a secure, password protected lab imaging database.  Images may also be stored in the clinical 


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center PACS. The lab imaging database will be stored and maintained in the Molecular 
Imaging Program facilities. Personal identifiers will not be used when storing data.  
NCI Molecular Imaging Program may exchange anonymized clinical data with working 
groups, and qualified investigators.  The anonymized image data will be stored in an existing 
secure off-site imaging database (EXEC PACS) and these images may be shared with 
researchers at other institutions. 
During the one year follow-up period, the patient’s PSA levels and prostate cancer related 
medical history, biopsy results, imaging studies and will be collected (reports and CD copies of 
the imaging studies). 
 
12.1.2 Safety Data  
The following safety data will be collected and evaluated according to the Study Calendar 
(Section 8.1.1): 
• Clinical laboratory variables: CBC, acute care panel, hepatic panel 
• Vital signs: systolic and diastolic BP, heart rate, body temperature, and respiration rate 
• Physical examination 
• Injection site monitoring 
• Pre-administration events (baseline signs and symptoms) 
• AEs 
SAEs will be recorded if they occurred as follows: 
• After a subject first received 18F DCFBC and throughout the subject’s follow-up period, 
• During the subject’s follow up period, and for which a causal relationship to 18F 
DCFBC cannot be ruled out. 
Interpretation and follow-up of abnormal results will be done on a case by case basis in 
conjunction with the individual clinical situation.  Any clinically significant abnormal finding, 
or change in one that represents a worsening from baseline, is an AE.  Once a decision is 
reached to report a finding as an AE, the investigator is required to follow the procedure 
described for AE notification.  
12.1.3 Imaging Data 
Extracted imaging data include: 
(1) PET imaging data will include SUV for each region of interest 
(2) All image data will be stored on a secure server, with access limited to credentialed 
users.  This will permit flexible numeric raw data extraction for quantitative analysis 
and creation of summary data reports. 


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(3) Anonymized image data from this study will be stored in a secure database that it is 
administered by the Cancer Imaging Program, NCI.  The data may be shared with 
research collaborators to improve upon current methods of image analysis. The 
database is password protected and access is only given to qualifying collaborators.  
Imaging findings for Na18F PET/CT will be dictated into the PACS system similar to other 
clinical radiologic studies, but dictations for 18F DCFBC PET/CT will only reflect the 
radiotracer dose, injection site and a statement indicating that the scan is for research purposes 
only. 
12.2 Toxicity Criteria 
The following adverse event management guidelines are intended to ensure the safety of each 
patient while on the study.  The descriptions and grading scales found in the revised NCI 
Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for 
AE reporting.  All appropriate treatment areas should have access to a copy of the CTCAE 
version 4.0.  A copy of the CTCAE version 4.0 can be downloaded from the CTEP web site 
(http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_40). 
13 Biospecimen Collection  
13.1 Tissue Samples (Arm 1) 
All tissue specimens (slide specimens) will have been obtained during the standard of care 
radical prostatectomy or biopsy under the NIH routine clinical protocol (part of the eligibility 
criteria for Arm 1) which includes:  barcoding and labeling as follows:   
Tissue samples will be shipped to a core biomarker laboratory analysis of PSMA expression by 
immunohistochemistry. Additional exploratory biomarker assessments may be conducted on 
tissue specimens to provide further information regarding correlation of tumor hypoxia and 
uptake of18F DCFBC depicted by PET/CT.   
Following completion of the core biomarker laboratory assessments, the PI, lead associate PI, 
one of the associate PIs or an appropriate designee will be responsible for collection of tissue 
specimens from the laboratories and return of specimens to NCI.   
Upon return of specimens to the NCI and following completion of this study, samples will 
remain in storage at NCI. Access to these samples will only be granted following IRB approval 
of an additional protocol, granting the rights to use the material.  
If, at any time, a subject withdraws from the study and does not wish for their existing samples 
to be utilized, the individual must provide a written request. Following receipt of this request, 
the samples will be destroyed (or returned to the patient, if so requested), and reported as such 
to the IRB. Any samples lost (in transit or by a researcher) or destroyed due to unknown 
sample integrity (i.e. broken freezer allows for extensive sample thawing, etc.) will be reported 
as such to the IRB. 


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Sample barcodes are linked to patient demographics and limited clinical information. This 
information will only be provided to investigators listed on this protocol, via registered use of 
the Patient Sample Data Management System (PSDMS). It is critical that the sample remains 
linked to patient information such as race, age, dates of diagnosis and death, and histological 
information about the tumor, in order to correlate genotype with these variables. 
13.2 Blood Samples 
Blood samples will be collected for screening and on-study clinical laboratory safety 
assessments.  All blood samples will be processed and handled in accordance with standard 
laboratory procedures.  All samples will be analyzed at the NCI Clinical Center laboratory. 
14 STATISTICAL CONSIDERATIONS 
14.1 Primary Analysis 
This is a single site three-arm pilot study, where prostate cancer patients are enrolled into 
different arms according to their disease types: localized (Arm 1), recurrent (Arm 2) or 
metastatic (Arm 3). The primary objective of this study is to assess the ability of 18F-DCFBC to 
identify sites of localized, recurrent and metastatic prostate cancer. To achieve this goal, 18F-
DCFBC PET/CT and conventional imaging will be used to identify positive suspected sites, 
and the proportion of positive concordance will be used to assess the performance of 18F-
DCFBC. In a recent study (Cho et al., 2012), 32 positive suspected sites in five prostate cancer 
patients with metastasis were identified by 18F-DCFBC PET/CT  with 21 concordant on both 
18F-DCFBC PET/CT and conventional imaging. At the individual level, the number of positive 
suspected sites ranged from 2 to 12 with the patient-specific concordance rate ranging from 0 
to 100%.  The overall concordance rate which was the average of individual-specific estimates 
across patients equaled 64% with corresponding standard deviation equal to 43%.  For the new 
study, assume that for patients in Arm 1 and Arm 3, the mean concordance rate is 70% with 
43% standard deviation as observed in Cho et al. With 12 evaluable patients in Arm 1, the 90% 
expected confidence interval for the mean concordance rate is (0.50, 0.90).  With 20 evaluable 
patients in Arm 3, the 90% expected confidence interval for the mean concordance rate is 
(0.54, 0.86).  For patients in Arm 2 (recurrent disease), it is unlikely to identify suspected 
lesions by conventional imaging at the baseline. These patients will be followed according to 
the protocol.   
Amendment E Addendum:  
Sensitivity of 18F-DCFBC uptake in prostate cancer patients in Arm 2 is evaluated by its ability 
in differentiating mean values of PSA between PET-CT positive and PET-CT negative 
patients. To this end, the current study with sample size 35 for Arm 2 is under-powered to 
detect a sizeable mean difference in PSA between the two groups. Based on the preliminary 
data of the study, log-transformed PSA is approximately normally distributed with standard 
deviation equal to 1.3. Assume 1:2 allocation of PET-CT negative vs. PET-CT positive 


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patients. The current study has only 48% power to detect a 2.5-fold geometric mean ratio in 
PSA between the two groups at the 5% significance level using a two-sided Wilcoxon test. To 
achieve 80% power, 26 PET-CT negative and 52 PET-CT positive patients are required. These 
results are based on 2000 Monte-Carlo samples from the normal distributions. Under the 
alternative hypothesis, log (PSA) is assumed to follow a normal distribution with mean (SD) 
equal to 0.06 (1.3) and 0.98 (1.3) for the PET-CT negative and PET-CT positive group, 
respectively. The mean difference of 0.92 (=0.98-0.06) in log scale of PSA corresponds to a 
2.5-fold geometric mean ratio in the original scale.  
In order to allow for the possibility of a small number of unevaluable patients, the accrual 
ceiling will be set at 15, 85 and 25, yielding a target ceiling of 125 patients for this study. 
14.2 Secondary Analysis 
For patients with localized disease, the diagnostic accuracy of 18F-DCFBC PET/CT will be 
compared with multiparametric MRI using the sector-based analysis.  Patient-specific 
sensitivity and specificity will be estimated and differences in sensitivity and specificity 
between different modalities will be tested by the Wilcoxon signed-rank test. Change of 18F-
DCFBC uptake for patients with metastatic disease over time will be estimated by the linear 
mixed effect model where random intercept will be used to account for the intra-patient 
correlation of longitudinal 18F-DCFBC uptake. In addition, in patients with metastatic prostate 
cancer to bone, the uptake of 18F-DCFBC will be correlated with the uptake of the emerging 
gold standard, 18F Sodium Fluoride PET/CT by the Spearman rank correlation. 
14.3 Interim Futility Analysis and Early Stopping Rule 
To avoid excessive expense and radiation exposure, if 18F-DCFBC PET/CT is not successful in 
identifying lesions, we implement the following interim futility analysis and early stopping 
rule. 
We plan to stop the protocol if the first 5 patients with soft tissue lesions greater than 1 cm 
have negative uptake (defined as tumor uptake less than adjacent background soft tissue, or 
blood pool for lymph nodes). Otherwise, a separate interim analysis for Arm 1 and Arm 3 will 
be carried out after 8 patients in each arm have been accrued. These will be independent 
interim analyses for each arm and only affect the given arm. If the mean PET-positive rate, 
defined as the average of patient-specific PET-positive rate among the positive sites identified 
by the conventional imaging, is less than 60%, the study would be declared futile, otherwise 
the study would proceed with accrual. Assuming the standard deviation of patient-specific 
PET-positive rate is 0.30, the probability of stopping for futility is 83% when the true PET-
positive rate is 0.5 and 17% when the true PET-positive rate is 0.70.  Since Arm 2 will by 
criteria not have lesions on conventional imaging, they are excluded from this interim analysis 
and early stopping rule. 
14.4 Sample Size and Accrual Rate 
The sample size for this single site pilot three-arm study is targeted at 12, 78 and 20 evaluable 
patients in Arm 1, Arm 2 and Arm 3, respectively. In order to allow for a small number of 


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nonevaluable patients, the accrual ceiling will be set at 125.  Assuming the accrual rate is 5-6 
patients per month, the total length of accrual period for this study will be about 24 months. 
 
15 SAFETY REPORTING REQUIREMENTS/DATA AND SAFETY MONITORING 
PLAN for NCI IRB 
15.1 Definitions 
15.1.1 Suspected adverse reaction 
Suspected adverse reaction means any adverse event for which there is a reasonable possibility 
that the drug caused the adverse event. For the purposes of IND safety reporting, ‘reasonable 
possibility’ means there is evidence to suggest a causal relationship between the drug and the 
adverse event. A suspected adverse reaction implies a lesser degree of certainty about causality 
than adverse reaction, which means any adverse event caused by a drug. 
15.1.2 Unexpected adverse reaction 
An adverse event or suspected adverse reaction is considered “unexpected” if it is not listed in 
the investigator brochure or is not listed at the specificity or severity that has been observed; or, 
if an investigator brochure is not required or available, is not consistent with the risk 
information described in the general investigational plan or elsewhere in the current 
application. "Unexpected” also refers to adverse events or suspected adverse reactions that are 
mentioned in the investigator brochure as occurring with a class of drugs or as anticipated from 
the pharmacological properties of the drug, but are not specifically mentioned as occurring 
with the particular drug under investigation. 
15.1.3 Serious  
An Unanticipated Problem or Protocol Deviation is serious if it meets the definition of a 
Serious Adverse Event or if it compromises the safety, welfare or rights of subjects or others. 
15.1.4 Serious Adverse Event 
An adverse event or suspected adverse reaction is considered serious if in the view of the 
investigator or the sponsor, it results in any of the following: 
• 
Death, 
• 
A life-threatening adverse drug experience 
• 
Inpatient hospitalization or prolongation of existing hospitalization 
• 
Persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
• 
A congenital anomaly/birth defect. 
• 
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered a serious adverse drug experience when, based upon 
appropriate medical judgment, they may jeopardize the patient or subject and may 
require medical or surgical intervention to prevent one of the outcomes listed in this 
definition. 


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15.1.5 Disability 
 A substantial disruption of a person’s ability to conduct normal life functions. 
15.1.6 Life-threatening adverse drug experience 
Any adverse event or suspected adverse reaction that places the patient or subject, in the view 
of the investigator or sponsor, at immediate risk of death from the reaction as it occurred, i.e., it 
does not include a reaction that had it occurred in a more severe form, might have caused 
death. 
15.1.7 Protocol Deviation (NIH Definition) 
Any change, divergence, or departure from the IRB-approved research protocol.   
15.1.8 Non-compliance (NIH Definition) 
The failure to comply with applicable NIH Human Research Protections Program (HRPP) 
policies, IRB requirements, or regulatory requirements for the protection of human research 
subjects. 
15.1.9 Unanticipated Problem 
Any incident, experience, or outcome that: 
•  Is unexpected in terms of nature, severity, or frequency in relation to  
(a) the research risks that are described in the IRB-approved research protocol and 
informed consent document; Investigator’s Brochure or other study documents, and 
(b) the characteristics of the subject population being studied; AND 
• Is related or possibly related to participation in the research; AND 
• Suggests that the research places subjects or others at a greater risk of harm (including 
physical, psychological, economic, or social harm) than was previously known or 
recognized. 
15.2 NCI-IRB Reporting 
15.2.1 NCI-IRB Expedited Reporting of Unanticipated Problems and Deaths 
The Protocol PI will report to the NCI-IRB: 
• All deaths, except deaths due to progressive disease  
• All Protocol Deviations 
• All Unanticipated Problems 
• All serious non-compliance 
Reports must be received by the NCI-IRB within 7 working days of PI awareness via iRIS. 
15.3 NCI-IRB Requirements for PI Reporting at Continuing Review 
The protocol PI will report to the NCI-IRB:  


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1. A summary of all protocol deviations in a tabular format to include the date the 
deviation occurred, a brief description of the deviation and any corrective action. 
2. A summary of any instances of non-compliance 
3. A tabular summary of the following adverse events: 
• All Grade 2 unexpected events that are possibly, probably or definitely related to 
the research;  
• All Grade 3 and 4 events that are possibly, probably or definitely related to the 
research;  
• All Grade 5 events regardless of attribution;  
• All Serious Events regardless of attribution.  
NOTE: Grade 1 events are not required to be reported. 
15.3.1 NCI-IRB Reporting of IND Safety Reports 
Only IND Safety Reports that meet the definition of an unanticipated problem will need to be 
reported to the NCI IRB. 
15.4 Data and Safety Monitoring Plan 
15.4.1 Principal Investigator/Research Team 
The principal investigator or appropriate designee and research nurse will monitor the study for 
AEs. 
This study will not have a formal data safety monitoring plan (DSMP), however, the principal 
investigator and Lead Associate Investigator will re-evaluate the protocol after each patient.   
The principal investigator reserves the right to terminate the study on safety grounds. If 3 study 
subjects experience ≥ grade 2 18F DCFBC –possibly or definitely related SAEs then the study 
will be terminated.  Before terminating the study, the investigator will ensure that a review of 
the overall risk/benefit analysis confirms the balance to be no longer acceptable.  Should 
termination be necessary, the PI will arrange the relevant procedures, which will include 
informing the IRB, and the FDA and other relevant local and national authorities.  On 
termination of the study, the investigator will assure that adequate consideration is given to the 
protection of enrolled subjects’ interests.  Termination of the study will be considered in the 
event of significant safety findings occurring at any time during the performance of the study. 
Adverse events will be reported as required above.  Any safety concerns, new information that 
might affect either the ethical and or scientific conduct of the trial, or protocol deviations will 
be immediately reported to the IRB using iRIS.  
The principal investigator will review adverse event and response data on each patient to 
ensure safety and data accuracy. The principal investigator will personally conduct or supervise 
the investigation and provide appropriate delegation of responsibilities to other members of the 
research staff. 


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16 HUMAN SUBJECTS PROTECTION 
16.1 Rationale for Subject Selection 
The patient population in whom this disease occurs is adult males. All ethnic groups/ race 
categories would be represented as they are represented in the disease as a whole.  Cognitively 
impaired individuals will not be included in this study if they are unable to understand the 
informed consent.  Physically impaired persons who otherwise satisfy eligibility criteria will be 
included in this study.  This study is considered more than minimal risk to subjects and no 
direct benefits to the patient are expected. We anticipate that a thorough discussion of the study 
at the time informed consent is obtained will minimize any susceptibility to undue influences 
and unnecessary risks to research subjects. 
16.2 Participation of Children 
Children will not be considered as research subjects for this study as this disease has never 
been documented to occur in children. 
16.3 Evaluation of Benefits and Risks/Discomforts 
Risks and discomforts of the experimental procedure are expected to be low and related to the 
risks of 18F DCFBC, and PET/CT imaging.  Most complications are expected to be minor and 
require no treatment. 
Risks and discomforts associated with 18F DCFBC PET/CT imaging are discomfort of an IV 
placement and the theoretical effects of the amount of additional radiation exposure.  The 
maximum effective dose is 2.4 rem for Arm 1 and for Arm 2 and 5.9 rem for Arm 3, which 
exceeds the NIH Radiation Safety Committee’s guidelines of 5.0 rem per year for adults. The 
benefits of the study for this group with metastatic cancer outweigh the potential radiation 
risks. The higher dosage for Arm 3 is due to the inclusion of F-Na PET/CT at baseline and 
follow-up. A follow-up 18F DCFBC PET/CT image also accounts for Arm 3’s higher dose. The 
activity of F18 FDCFBC is 8 mCi and the activity of F18 NaF is 3 mCi. In this study, the 
subject will be required to lie still on his back for up to 45- minutes at a time, and this might 
produce some discomfort.  
16.4 Risks/Benefits Analysis 
The risks of participation are low based on the very low doses used and prior knowledge of a 
low rate of AEs for 18F DCFBC.  No direct benefits to the subject are anticipated; however, the 
knowledge derived from the study could have broader implications in the field.  As the 
significance of a 18F DCFBC-depicted lesion is uncertain, treatment decisions will not be based 
on 18F DCFBC PET/CT findings.  Further evaluation with standard of care diagnostic imaging 
and/or biopsy will be performed at the discretion of the referring physician.  The decision to 
pursue further imaging or pathological confirmation and the methods of doing so will be left to 
the referring clinician and is not dictated by this imaging protocol. 


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16.5 Consent and Assent Process and Documentation 
The subject will be informed of the study by a member of the study team.  Written and oral 
information about the study in a language understandable by the subject will be given to all 
subjects.  The study will be explained in detail and the consent form and protocol (if requested) 
will be provided to the subject to take home (if desired) for consideration.  If the subject has 
any questions they will be answered at the time of initial protocol discussion or later by 
telephone.  Each subject’s willingness to participate in the study will be documented in a 
signed and dated informed consent form before any procedures or assessments are done and 
after the aims, methods, anticipated benefits, potential hazards, and insurance arrangements in 
force are explained.  It will also be explained to the subjects that they are free to refuse entry 
into the study and free to withdraw from the study at any time without prejudice to future 
treatment.  The informed consent process will be documented in the subject's medical record 
and the investigator will sign, and date the informed consent form after the subject and/or legal 
representative has signed and dated it.  The investigator(s) will keep the original consent forms 
and copies will be given to the subjects.  Informed consent may be obtained from the patient by 
the PI, an associate PI or any clinical designee credentialed to obtain informed consent for any 
procedure.  
 


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17 References 
1. 
Kinoshita, Y., et al., Expression of Prostate-Specific Membrane Antigen in Normal and 
Malignant Human Tissues. World Journal of Surgery, 2006. 30(4): p. 628-636. 
2. 
Milowsky, M.I., et al., Vascular targeted therapy with anti-prostate-specific membrane 
antigen monoclonal antibody J591 in advanced solid tumors. J Clin Oncol, 2007. 25(5): 
p. 540-7. 
3. 
Sokoloff, R.L., et al., A dual-monoclonal sandwich assay for prostate-specific membrane 
antigen: Levels in tissues, seminal fluid and urine. The Prostate, 2000. 43(2): p. 150-157. 
4. 
Trover, J.K., M.L. Beckett, and G.L. Wright, Detection and characterization of the 
prostate-specific membrane antigen (PSMA) in tissue extracts and body fluids. 
International Journal of Cancer, 1995. 62(5): p. 552-558. 
5. 
Liu, H., et al., Constitutive and antibody-induced internalization of prostate-specific 
membrane antigen. Cancer Res, 1998. 58(18): p. 4055-60. 
6. 
Troyer, J.K., M.L. Beckett, and G.L. Wright, Jr., Location of prostate-specific membrane 
antigen in the LNCaP prostate carcinoma cell line. Prostate, 1997. 30(4): p. 232-42. 
7. 
Elsasser-Beile, U., et al., PET imaging of prostate cancer xenografts with a highly 
specific antibody against the prostate-specific membrane antigen. J Nucl Med, 2009. 
50(4): p. 606-11. 
8. 
Bander, N.H., et al., Targeting Metastatic Prostate Cancer With Radiolabeled 
Monoclonal Antibody J591 to the Extracellular Domain of Prostate Specific Membrane 
Antigen. The Journal of Urology, 2003. 170(5): p. 1717-1721. 
9. 
Nargund, V., et al., Imaging with radiolabelled monoclonal antibody (MUJ591) to 
prostate-specific membrane antigen in staging of clinically localized prostatic 
carcinoma: comparison with clinical, surgical and histological staging. BJU 
international, 2005. 95(9): p. 1232-6. 
10. 
Evans, M.J., et al., Noninvasive measurement of androgen receptor signaling with a 
positron-emitting radiopharmaceutical that targets prostate-specific membrane antigen. 
Proceedings of the National Academy of Sciences of the United States of America, 2011. 
108(23): p. 9578-82. 
11. 
Foss, C.A., et al., Radiolabeled small-molecule ligands for prostate-specific membrane 
antigen: in vivo imaging in experimental models of prostate cancer. Clinical cancer 
research : an official journal of the American Association for Cancer Research, 2005. 
11(11): p. 4022-8. 
12. 
Banerjee, S.R., et al., 68Ga-labeled inhibitors of prostate-specific membrane antigen 
(PSMA) for imaging prostate cancer. Journal of Medicinal Chemistry, 2010. 53(14): p. 
5333-41. 
13. 
Barrett, J.A., et al., First-in-Man Evaluation of Two High-Affinity PSMA-Avid Small 
Molecules for Imaging Prostate Cancer. Journal of nuclear medicine : official 
publication, Society of Nuclear Medicine, 2013. 
14. 
Mease, R.C., et al., N-[N-[(S)-1,3-Dicarboxypropyl]carbamoyl]-4-[18F]fluorobenzyl-L-
cysteine, [18F]DCFBC: a new imaging probe for prostate cancer. Clinical cancer 
research : an official journal of the American Association for Cancer Research, 2008. 
14(10): p. 3036-43. 
15. 
Cho, S.Y., et al., Biodistribution, Tumor Detection, and Radiation Dosimetry of 18F-
DCFBC, a Low-Molecular-Weight Inhibitor of Prostate-Specific Membrane Antigen, in 


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Patients with Metastatic Prostate Cancer. Journal of nuclear medicine : official 
publication, Society of Nuclear Medicine, 2012. 53(12): p. 1883-91. 
16. 
Stabin, M.G. and J.A. Siegel, Physical models and dose factors for use in internal dose 
assessment. Health Phys, 2003. 85(3): p. 294-310. 
17.       Mertens LS, Bruin NM, Vegt E, et al. Catheter-assisted 18F-FDG-PET/CT imaging of 
primary bladder cancer: a prospective study. Nucl Med Commun 2012;33:1195-201. 
18.       Koyama K, Okamura T, Kawabe J, et al. Evaluation of 18F-FDG PET with bladder 
irrigation in patients with uterine and ovarian tumors. J Nucl Med 2003;44:353-8. 
 
 


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18 APPENDICES 
18.1 APPENDIX A: Performance Status Criteria 
ECOG Performance Status Scale 
Grade 
Descriptions 
0 
Normal activity.  Fully active, able to carry on all pre-
disease performance without restriction. 
1 
Symptoms, but ambulatory.  Restricted in physically 
strenuous activity, but ambulatory and able to carry out 
work of a light or sedentary nature (e.g., light housework, 
office work). 
2 
In bed <50% of the time.  Ambulatory and capable of all 
self-care, but unable to carry out any work activities.  Up 
and about more than 50% of waking hours. 
3 
In bed >50% of the time.  Capable of only limited self-
care, confined to bed or chair more than 50% of waking 
hours. 
4 
100% bedridden.  Completely disabled.  Cannot carry on 
any self-care.  Totally confined to bed or chair. 
5 
Dead. 
 


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18.2 Appendix B: F18 DCFBC Order Form  
 
 

ICF_001.pdf: 
MEDICAL RECORD 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
• 
Adult Patient or 
• Parent, for Minor Patient 
INSTITUTE: 
National Cancer Institute 
STUDY NUMBER: 
14-C-0140 
PRINCIPAL INVESTIGATOR: 
Maria Liza Lindenberg, M.D. 
STUDY TITLE:  
A  Pilot Study of 18F-DCFBC PET/CT in Prostate Cancer 
 
Continuing Review Approved by the IRB on 04/25/16 
Amendment Approved by the IRB on 12/14/15 (E) 
 
Date posted to web: 05/13/16 
Standard 
PATIENT IDENTIFICATION 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH 
STUDY 
•   Adult Patient or    •  Parent, for Minor Patient 
NIH-2514-1 (07-09) P.A.: 09-25-0099 
File in Section 4: Protocol Consent (1) 
 
 
 
INTRODUCTION 
We invite you to take part in a research study at the National Institutes of Health (NIH). 
First, we want you to know that: 
Taking part in NIH research is entirely voluntary.  
You may choose not to take part, or you may withdraw from the study at any time.  In 
either case, you will not lose any benefits to which you are otherwise entitled.  However, 
to receive care at the NIH, you must be taking part in a study or be under evaluation for 
study participation. 
You may receive no benefit from taking part. The research may give us knowledge that 
may help people in the future. 
Second, some people have personal, religious or ethical beliefs that may limit the kinds of 
medical or research treatments they would want to receive (such as blood transfusions). If you 
have such beliefs, please discuss them with your NIH doctors or research team before you agree 
to the study. 
Now we will describe this research study. Before you decide to take part, please take as much 
time as you need to ask any questions and discuss this study with anyone at NIH, or with family, 
friends or your personal physician or other health professional. 
Why is this study being done?  
Prostate cancer is the second leading cause of cancer deaths in American men. Currently there 
are not many options available to image this type of cancer. In this study we will use an 
experimental radiotracer called, 18F-DCFBC, to see if it can identify sites of prostate cancer in 
you.  


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:14-C-0140 
CONTINUATION: page 2 of 11 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
Why are you being asked to take part in this study? 
You are being invited to take part in this research study because you have prostate cancer that 
has been newly diagnosed, relapsed, or has spread outside the prostate gland.  
How many people will take part in this study?  
Up to 125 men will be included in this study. 
Description of Research Study 
This research will determine if the experimental radiotracer, 18F-DCFBC, can identify sites of 
prostate cancer in the body. The study participants will be divided into 3 groups.  The first group 
will be patients with cancer only in the prostate. The second group will be patients who have had 
their prostate removed or had radiation therapy and now have a rising PSA without other 
evidence for disease. The third group will be those patients with verified metastatic disease. All 
patients will be imaged with 18F-DCFBC. Subjects in the first group of patients will have a MRI 
performed. If you are in the third group of patients you will also be imaged with 18F-NaF for 
evaluation of bone disease. 
What will happen if you take part in this research study?   
Before you begin the study, screening labs requiring about 3 teaspoons of blood, and a limited 
physical exam and medical history will be done. Your doctor will review all the eligibility 
requirements to ensure you meet all the criteria before you enter the study. If you are determined 
to be eligible for this study, you will then be scheduled to return for the study injection and 
imaging scans. 
Imaging Studies (Scans)  
For subjects in group 1 only: 
MRI Imaging  
An MRI scan will be performed on a 3 Tesla magnet in the Molecular Imaging Clinic. “Tesla” is 
the unit of magnetic field strength. There are no known health effects from MRI scanning at any 
field strength including 3 Tesla, which is the highest strength magnetic currently in routine 
clinical use. MRI does not use any ionizing radiation (such as x-rays). In order to better see your 
prostate with MRI, a tube, known as an endorectal coil, will be placed in your rectum. Additional 
coils may be wrapped around the outside of your pelvis to further improve the quality of the 
scan. The MRI scan usually takes 75-90 minutes. You will need to lie still on the scanning table 
during that time. An intravenous line will be started and a contrast agent called Gadolinium 
chelate will be injected. This provides additional information about your prostate.  Gadolinium 
chelate is FDA approved and is routinely used in MRI exams with very few side effects. You 
will receive more information about your MRI scan when you visit the Molecular Imaging Clinic 
and you may ask questions at any time. In addition, you should ask your doctor any questions 
you have concerning this study.  


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:14-C-0140 
CONTINUATION: page 3 of 11 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
PET/CT Imaging 
For subjects in group 1 & group 2: 
You will receive an IV injection of 18F-DCFBC over 10-20 seconds. A dynamic PET/CT will be 
performed immediately after the 18F-DCFBC injection. This scan will last about 45 minutes. 
About an hour from the 18F-DCFBC injection, a whole body PET/CT will be performed. This 
scan will last about 50 minutes. Approximately 2 hours from the 18F-DCFBC injection the last 
whole body PET/CT scan will be done. The scan will also last about 50 minutes.  
For subjects in group 3 only:  
You will receive an IV injection of 18F DCFBC over 10-20 seconds. A whole body PET/CT will 
be performed about 1 hour after the 18F-DCFBC injection. This scan will last about 50 minutes. 
Another whole body PET/CT will be done approximately 2 hours from the 18F-DCFBC injection. 
This scan will also last about 50 minutes. 
For subjects in group 2 only who have had their prostate gland removed: 
A urinary catheter will be inserted into your bladder if needed, to improve our ability to view 
your bladder and the nearby anatomy during PET/CT imaging.  The catheter will be attached to 
an irrigation system that allows for continuous rinsing and drainage of your bladder.   
The urinary catheter is a thin hollow tube that is placed into the bladder to drain urine from your 
bladder. This tube has 3 separated channels within it.  One channel allows for the urine to drain 
from the bladder into a fluid collection bag.  The second channel has a valve on the outside end 
and connects to a balloon at the tip of the catheter.  The balloon is inflated with sterile water to 
keep the catheter in place.  The third channel allows for fluids to be put into your bladder.  If you 
cannot tolerate this type of urinary catheter, we will use a catheter with 2 separate channels that 
only allows for drainage of urine from bladder. If you are not able to tolerate catheter placement, 
you will be asked to urinate frequently during the procedure.  
 
The male urethra is long compared to the female urethra. A catheter is placed while lying down. 
The urethra and the surrounding areas are cleaned with a cotton-ball dipped in antiseptic 
solution. Beginning at the urethra, the cleansing is performed in a circular motion, moving 
outward to the surrounding areas.  The urinary catheter, lubricated with water-soluble jelly, is 
inserted into the bladder through the urethra.  Once the catheter is passed, the balloon is in the 
bladder. It is then slowly inflated with about 10cc of  air using a syringe. Inflating the balloon 
should not be painful.  At this time, urine, if present in the bladder, should flow back through the 
catheter and into the sterile drainage bag.   
For subjects in group 3 only: 
For patients in group 3 with known metastasis, an additional PET/CT scan with 18F-NaF will be 
performed to evaluate bone disease within 21 days of the 18F-DCFBC PET/CT.   


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:14-C-0140 
CONTINUATION: page 4 of 11 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
Patients in group 3 will also be asked to repeat the 18F-NaF PET/CT and 18F-DCFBC PET/CT. 
These will scans will be performed 4-6 months after the initial scans.   
PET/CT Imaging Session: 
During this scanning procedure, you will be asked to lie on your back on the scanner table and a 
low dose transmission CT scanner will be performed.  It is important that you remain very still 
during these scans. The entire imaging session is expected to take not more than 3 hours and 
breaks will be permitted as needed. Interval monitoring of vital signs and for possible adverse 
events will be performed through the study.  
When you are finished with each imaging scan, a member of the study team will contact you 
within 1-3 days for follow-up. 
PET/MRI Imaging Session: 
During this scanning procedure, you will be asked to lie on your back on the PET/MRI scanner 
table and PET/MRI imaging of your whole body will be performed simultaneously.  It is 
important that you remain very still during these scans.  In order to better see your prostate with 
MRI, a tube, known as an endorectal coil, may be placed in your rectum. Additional coils may be 
wrapped around the outside of your pelvis to further improve the quality of the scan. The entire 
imaging session is expected to take about 1 hour.  
Prostatectomy: (group 1 only) 
If you are in group 1 you may have surgery (a procedure called a prostatectomy) to remove your 
prostate gland or a biopsy to remove some prostate tissue. This procedure will be standard of 
care and is not a part of this protocol. Tissue collected during your surgery to remove your 
prostate will be evaluated at NIH just as it would be if you were not participating in this trial.  
Birth Control 
Due to the unknown effects on sperm or the fetus, it is advisable to practice careful 
contraception.  If you are a male with a female partner who has the ability to get pregnant, you 
must agree to use a barrier method of birth control during the study and 2 months following the 
injection of the study agent.  Your partner must also agree to use another method of birth control 
while you are on the study. 
If you think that your partner is pregnant, you should tell your study doctor or nurse at once. 
Effective forms of birth control include: 
 Abstinence 
 Intrauterine device (IUD) 
 Hormonal [birth control pills, injections, or implants] 
 Tubal ligation 
 Vasectomy 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:14-C-0140 
CONTINUATION: page 5 of 11 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
Alternative Approaches or Treatments 
There are no alternative approaches or treatments. You are not required to participate in this 
study.  If you decide not to participate, it will not alter your planned treatment.   
What other choices do I have if I do not take part in this study?  
You are not obligated to participate in this study. If you decide not to participate, it will not alter 
your planned treatment.  
Risks or Discomforts of Participation 
What side effects or risks can I expect from being in this study?  
Risks of MRI (For subjects in group 1 only) 
Having an MRI requires that you lie still with part of you or all of you inside a tube shaped 
machine for about 45 minutes to an hour. Even with the ear plugs we give you it can be noisy 
with loud clicking and thumping sounds, which bothers some people. Some people may feel 
‘closed in’ or ‘trapped’ (even though they are being closely watched and are quite safe). This is 
called claustrophobia. Cool air will surround you, and the room is large and brightly lit to help 
avoid claustrophobia. You may ask your physician for a mild sedative for the procedure if you 
think it will help. If you take a sedative you must not drive a vehicle until it wears off after the 
MRI.  
MRI scans cannot be done on people who have: 
 a cardiac pacemaker,  
 neural pacemaker,  
 surgical metal clips in the brain or on blood vessels,  
 cochlear implants,  
 or foreign metal objects within the eye.   
At the time of your MRI, you will be asked about these things.   
Risks from Gadolinium 
Gadolinium has been generally safe when given to people as a contrast agent for MRI scans.  
Side effects from Gadolinium may occur in this trial.  If they do happen it is usually right around 
the time of injection, which is why you will be closely watched at that time, and promptly treated 
if necessary. These effects include:  
 coolness in the arm during injection 
 whole body allergic reactions, which can range from mild to serious or life threatening 
(this is called anaphylaxis),  
 low blood pressure, which can lead to becoming unconscious (fainting, passing-out) 
 feeling hot, nausea, headache 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:14-C-0140 
CONTINUATION: page 6 of 11 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
Potential discomforts from the IV and injection of the radiotracer include  
 Mild pain and possible bruising at the injection site,  
 Discomfort from lying on a hard surface for about 90 minutes. 
 Infection at the IV site or infection in the blood  
 Leaking of the dose of 18F-DCFBC into the skin and tissue around the IV 
 Allergic reaction 
 Vasovagal reaction, a lowered blood pressure and heart rate during the IV insertion  
Risks of Urinary Catheter Insertion 
 The balloon can break while the catheter is being inserted. In this case, the catheter and 
all of the balloon fragments are removed. 
 The balloon does not inflate after it is in place. The balloon inflation is checked before 
inserting the catheter into the urethra and if it does not inflate after its placement into the 
bladder, it is removed and another urinary catheter is inserted. 
 Urine stops flowing into the bag. This is usually corrected by adjusting the positioning of 
the catheter and bag to allow urine flow within the catheter tube. 
 The urethra begins to bleed. A small amount of bleeding can be caused by irritation. This 
will be monitored 
 The urinary catheter may introduce an infection into the bladder. The risk of infection in 
the urine increases with the number of days the catheter is in place. 
 If the balloon is opened before the urinary catheter is completely inserted into the 
bladder, bleeding, and damage to the urethra can occur. To avoid this, the balloon is not 
inflated until the catheter is in the bladder.  
 Bladder spasms can occur when a catheter is placed. This is a sudden intense urge to 
urinate and can be painful. Often, urine will leak around the outside of the catheter when 
a spasm occurs. Medication can be prescribed for bladder spasms. 
Radiation Exposure:  
You will receive a small amount of radiation exposure that you would not otherwise receive.  
Radiation exposure is not necessary for your medical care and is for research purposes only.  
 
Using the standard way of describing radiation dose, from participating in this study subjects in 
groups one and two will receive one 18F-DCFBC PET/CT imaging session. The activity of F18 
FDCFBC is 8 mCi. Subjects in group one and two will receive up to 2.4 rem of radiation per 
year. Subjects in group three with known prostate cancer metastasis will undergo up to two 18F 
DCFBC PET/CTs and two 18F NaF PET/CTs.  The activity of F18 NaF is 3 mCi. The subjects in 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:14-C-0140 
CONTINUATION: page 7 of 11 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
this group will receive 5.9 rem of radiation per year which exceeds the NIH Radiation Safety 
Committee’s guidelines of 5.0 rem per year for adults.  
This calculated value is known as the “effective dose” and is used to relate the dose received by 
each organ to a single value.  For comparison, the average person in the United States receives a 
radiation exposure of 0.3 rem per year from natural background sources, such as from the sun, 
outer space, and from radioactive materials that are found naturally in the Earth’s air and soil.  
The effects of radiation exposure on humans have been studied for over 60 years.  In fact, these 
studies are the most extensive ever done of any potentially harmful agent that could affect 
humans.  In all these studies, no harmful effects were ever observed from the levels of radiation 
you will receive by taking part in this research study.  However, scientists disagree on whether 
radiation doses at these levels are harmful.  Even though no effects have been observed, some 
scientists believe that radiation can be harmful at any dose - even low doses such as those 
received during this research.  
If you would like more information about radiation and examples of exposure levels from other 
sources, please ask the investigator for a copy of the pamphlet called, An Introduction to 
Radiation for NIH Research Subjects. Please tell your doctor if you have taken part in other 
research studies or received any medical care at the NIH or other places/hospitals that used 
radiation.  This way we can make sure that you will not receive too much radiation.  Consider x-
rays taken in radiology departments, cardiac catheterization, and fluoroscopy as well as nuclear 
medicine scans in which radioactive materials were injected into your body. 
Results from the 18F-DCFBC PET/CT will be discussed with your NIH physician but is not 
intended for management decisions in your care. The ability of this agent to image the prostate in 
humans is not known and the scan may show findings that are different from the MRI. 
One Year Follow-up Period 
We will collect information related to your prostate cancer for one year after the completion of 
your last DCFBC PET/CT scan.  We will contact you and/or your treating physician to collect 
PSA levels and prostate cancer related medical history, biopsy results, and imaging study results 
(reports and CD copies of the imaging studies). 
Potential Benefits of Participation 
Are there benefits to taking part in this study?  
Since this an imaging study and NOT a treatment protocol, there are no direct benefits, although 
the knowledge gained from this study may help others in the future who have cancer.   


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:14-C-0140 
CONTINUATION: page 8 of 11 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
Research Subject’s Rights 
What are the costs of taking part in this study?  
If you choose to take part in the study, the following will apply, in keeping with the NIH policy: 
 
You will receive study treatment at no charge to you. This may include 
surgery, medicines, laboratory testing, x-rays or scans done at the 
Clinical Center, National Institutes of Health (NIH), or arranged for you 
by the research team to be done outside the Clinical Center, NIH if the 
study related treatment is not available at the NIH.  
 
There are limited funds available to cover the cost of some tests and 
procedures performed outside the Clinical Center, NIH.  You may have 
to pay for these costs if they are not covered by your insurance company. 
 
Medicines that are not part of the study treatment will not be provided or 
paid for by the Clinical Center, NIH. 
 
Once you have completed taking part in the study, medical care will no 
longer be provided by the Clinical Center, NIH. 
Will your medical information be kept private?  
We will do our best to make sure that the personal information in your medical record will be 
kept private.  However, we cannot guarantee total privacy.  Organizations that may look at 
and/or copy your medical records for research, quality assurance, and data analysis include: 
 The National Cancer Institute (NCI) and other government agencies, like the Food and 
Drug Administration (FDA), which are involved in keeping research safe for people. 
 National Cancer Institute Institutional Review Board 
 The study Sponsor, the NCI, or their agent(s).  
A description of this clinical trial will be available on http://www.Clinicaltrials.gov, as required 
by U.S. Law.  This Web site will not include information that can identify you.  At most the 
Web site will include a summary of the results.  You can search this Web site at any time.  
Stopping Rules 
Your doctor may decide to remove you from this study for the following reasons: 
 if he/she believes that it is in your best interest 
 if you have side effects from the imaging agent that your doctor thinks are too severe 
In this case, you will be informed of the reason why you are being taken off this study. 
You can stop taking part in the study at any time. However, if you decide to stop taking part in 
the study, we would like you to talk to the study doctor and your regular doctor first. 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:14-C-0140 
CONTINUATION: page 9 of 11 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
If you decide at any time to withdraw your consent to participate in the trial, we will not collect 
any additional medical information about you. However, according to FDA guidelines, 
information collected on you up to that point may still be provided to NCI or designated 
representatives. If you withdraw your consent and leave the trial, any samples of yours that have 
been obtained for the study and stored at the NCI can be destroyed upon request. However, any 
samples and data generated from the samples that have already been distributed to other 
researchers or placed in the research databases cannot be recalled and destroyed. 
 
Conflict of Interest 
The National Institutes of Health (NIH) reviews NIH staff researchers at least yearly for conflicts 
of interest. This process is detailed in a Protocol Review Guide.   You may ask your research 
team for a copy of the Protocol Review Guide or for more information.  Members of the research 
team who do not work for NIH are expected to follow these guidelines but they do not need to 
report their personal finances to the NIH. 
Members of the research team working on this study may have up to $15,000 of stock in the 
companies that make products used in this study.  This is allowed under federal rules and is not a 
conflict of interest.  


MEDICAL RECORD 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
• 
Adult Patient or 
• Parent, for Minor Patient 
STUDY NUMBER:14-C-0140 
CONTINUATION: page 10 of 11 pages 
 
PATIENT IDENTIFICATION 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH 
STUDY (Continuation Sheet) 
• 
Adult Patient or 
• Parent, for Minor Patient: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
OTHER PERTINENT INFORMATION 
1. 
Confidentiality.  When results of an NIH research study are reported in medical journals 
or at scientific meetings, the people who take part are not named and identified.  In most cases, 
the NIH will not release any information about your research involvement without your written 
permission.  However, if you sign a release of information form, for example, for an insurance 
company, the NIH will give the insurance company information from your medical record.  This 
information might affect (either favorably or unfavorably) the willingness of the insurance 
company to sell you insurance. 
The Federal Privacy Act protects the confidentiality of your NIH medical records.  However, you 
should know that the Act allows release of some information from your medical record without 
your permission, for example, if it is required by the Food and Drug Administration (FDA), 
members of Congress, law enforcement officials, or authorized hospital accreditation 
organizations. 
2. 
Policy Regarding Research-Related Injuries.  The Clinical Center will provide short-
term medical care for any injury resulting from your participation in research here.  In general, 
no long-term medical care or financial compensation for research-related injuries will be 
provided by the National Institutes of Health, the Clinical Center, or the Federal Government.  
However, you have the right to pursue legal remedy if you believe that your injury justifies such 
action. 
3. 
Payments.  The amount of payment to research volunteers is guided by the National 
Institutes of Health policies.  In general, patients are not paid for taking part in research studies at 
the National Institutes of Health.  Reimbursement of travel and subsistence will be offered 
consistent with NIH guidelines. 
4. 
Problems or Questions.  If you have any problems or questions about this study, or 
about your rights as a research participant, or about any research-related injury, contact the 
Principal Investigator, Maria Liza Lindenberg, M.D., Building 10, Room B3B402, Telephone:  
301- 443-0604. You may also call the Clinical Center Patient Representative at 301-496-2626.  
5. 
Consent Document.  Please keep a copy of this document in case you want to read it 
again. 


MEDICAL RECORD 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
• 
Adult Patient or 
• Parent, for Minor Patient 
STUDY NUMBER:14-C-0140 
CONTINUATION: page 11 of 11 pages 
 
PATIENT IDENTIFICATION 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH 
STUDY (Continuation Sheet) 
• 
Adult Patient or 
• Parent, for Minor Patient: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
 
 
COMPLETE APPROPRIATE ITEM(S) BELOW: 
A. Adult Patient’s Consent 
B. Parent’s Permission for Minor Patient. 
I have read the explanation about this study 
and have been given the opportunity to discuss 
it and to ask questions.  I hereby consent to 
take part in this study. 
I have read the explanation about this study 
and have been given the opportunity to discuss 
it and to ask questions.  I hereby give 
permission for my child to take part in this 
study.   
(Attach NIH 2514-2, Minor’s Assent, if 
applicable.) 
 
  
  
 
 
 
Signature of Adult Patient/ 
Legal Representative 
Date 
Signature of Parent(s)/ Guardian Date 
 
 
Print Name 
 
 
Print Name 
C. Child’s Verbal Assent (If Applicable) 
The information in the above consent was described to my child and my child agrees to 
participate in the study. 
 
  
  
 
Signature of Parent(s)/Guardian 
Date 
Print Name 
THIS CONSENT DOCUMENT HAS BEEN APPROVED FOR USE  
FROM APRIL 25, 2016 THROUGH APRIL 24, 2017.  
 
 
 
 
 
 
 
 
Signature of Investigator 
Date 
Signature of Witness 
Date 
 
 
Print Name 
 
 
Print Name