A Prospective Study of the RefleXion [18F]- DCFPyL PET-CT Subsystem Imaging Performance in Patients With Prostate Cancer
Phase: NA
Conditions: Prostate Carcinoma
Sponsor: City of Hope Medical Center

 
IRB 22189 
 
07/08/2022 
Packet : 02 
CITY OF HOPE NATIONAL MEDICAL CENTER 
1500 E. DUARTE ROAD 
DUARTE, CA 91010 
 
DEPARTMENT OF Radiation Oncology  
 
 
TITLE: A Prospective Study of the RefleXion [18F]- DCFPyL PET-CT Subsystem Imaging Performance in 
Patients with Prostate Cancer 
 
CITY OF HOPE PROTOCOL NUMBER/VERSION: IRB # 22189  
PROTOCOL DATE: 07/08/2022 
 
 
 
 
 
 
 
 
 
 
 
 
DATE(S)/ OF AMENDMENT(S)/REVISION(S): 
 
 
COH Initial Approval 
Protocol Dated 05/03/2022 
Packet: 00 
Amendment 01 
Protocol Dated 07/08/2022 
Packet: 01 
 
Amendment 02 at Continuation Protocol Dated 07/08/2022 
 
 
 
 
        Packet 02 
 
SITE:  
 
 
 
 
 
STAGE (If applicable): 
 
 
 
MODALITY:  
 
 
 
 
TYPE:  
 
 
 
 
 
 
PRINCIPAL INVESTIGATOR: 
 
Wong, Jeffrey, M.D. 
 
BIOSTATISTICIAN:  
 
 
Frankel, Paul, Ph.D. 
 
COLLABORATING INVESTIGATOR(S): 
Amini, Arya, M.D.  
Dandapani, Savita, M.D., Ph.D.  
Glaser, Scott, M.D.  
Han, Chunhui, Ph.D.  
Li, Rose, M.D., Ph.D.  
Liu, An, Ph.D.  
McGee, Heather, M.D., Ph.D.  
Sampath, Sagus, M.D.  
Williams, Terence, M.D.  
Yamauchi, Dave, M.D.  
 
 
 
PARTICIPATING CLINICIANS: 
 
NA 
 
COMMUNITY PRACTICE SITES: NA 

This document is confidential and for research purposes only. Distribute and use ONLY as authorized.  
 
 
City of Hope National Medical Center 
1500 E. Duarte Road 
Duarte, CA 91010 
Clinical Trial Protocol 
Protocol Title: A Prospective Study of the RefleXion [18F]- DCFPyL PET-CT Subsystem 
Imaging Performance in Patients with Prostate Cancer 
Version Date: 07/08/2022 
Protocol Version: 01 
 
City of Hope IRB #: 22189 
Agents: NA 
Sponsor Holder: City of Hope 
Funding Support/Industry Partner: RefleXion 
NCT Number: Pending 
Participating Sites: City of Hope (Duarte)  
Short Title RefleXion [18F]- DCFPyL PET-CT Subsystem Imaging 
Principal Investigator 
Jeffrey Y.C. Wong, MD 
City of Hope National Medical Center 
Dept. of Radiation Oncology 
T: 626-218-2247 
Email: jwong@coh.org 
 
 

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PROTOCOL TEAM 
 
Co-investigator 
Dave Yamauchi, MD 
City of Hope 
Chief, Division of Nuclear Medcine 
Dept. of Dianostic Radiology 
T: 626-218-8252 
Email: dyamauch@coh.org 
 
Co-Investigator 
Savita Dandapani, MD, PhD 
City of Hope 
Dept. of Radiation Oncology 
T: 626-218-2247 
Email: sdandapani@coh.org 
 
Co-investigator 
Maria Parayno, MD 
City of Hope 
Division of Nuclear Medcine 
Dept. of Dianostic Radiology 
T: 626-218-8252 
Email: mparayno@coh.org 
 
Co-Investigator 
Rose Li, MD, PhD 
City of Hope 
Dept. of Radiation Oncology 
T: 626-218-2247 
Email: yunroseli@coh.org 
 
Co-Investigator 
Scott Glaser, MD 
City of Hope 
Dept. of Radiation Oncology 
T: 626-218-2247 
Email: sglaser@coh.org  
Co-Investigator 
An Liu, PhD 
City of Hope 
Dept. of Radiation Oncology 
T: 626-218-2247 
Email: aliu@coh.org  
Co-Investigator 
Chunhui Han, PhD 
City of Hope 
Dept. of Radiation Oncology 
T: 626-218-2247 
Email: chan@coh.org  
 
Co-Investigator 
Arya Amini, MD 
City of Hope 
Dept. of Radiation Oncology 
T: 626-218-2247 
Email: aamini@coh.org  
 
Co-Investigator 
Heather McGee, MD, PhD 
City of Hope 
Dept. of Radiation Oncology 
T: 626-218-2247 
Email: hmcgee@coh.org 
 
Biostatisticion 
Paul Frankel, PhD 
City of Hope 
Dept. of Biostatistics 
T: 626-XXX_XXXX 
Email: pfrankel@coh.org 
 
Co-Investigator 
Sagus Sampath, MD 
City of Hope 
Dept. of Radiation Oncology 
T: 626-218-2247 
Email: ssampath@coh.org 
 
Co-Invesitagor 
Nayana Vora, MD 
City of Hope 
Dept. of Radiation Oncology 
T: 626-218-2247 
Email: nvora@coh.org  
 
 
 
 
 
 
 
Co-Investigator 
Terence Williams, MD PhD 
City of Hope 
Dept. of Radiation Oncology 
T: 626-218-2247 
Email: twilliams@coh.org 
 
 
 
  
 
 
 
 
 

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STUDY SCHEMA 
 

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PROTOCOL SYNOPSIS 
The RefleXion Medical Radiotherapy System (RMRS) is a hybrid imaging-therapy system that is FDA 
cleared (K190978) to deliver IMRT/SBRT/SRS external beam radiation therapy. It consists of 6 
megavoltage (MV) photon radiotherapy delivery, PET imaging hardware, kilovoltage (kV) X-ray CT 
imaging, and treatment planning subsystems. The system includes the capability of PET imaging when 
used in a research mode.  
Prostate-specific membrane antigen (PSMA) PET with 2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine-3-
carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid ([18F]-DCFPyL) has been approved for imaging 
PSMA- positive lesions in men with prostate cancer with either (1) suspected metastasis who are 
candidates for initial definitive therapy or (2) suspected recurrence based on elevated serum prostate-
specific antigen (PSA) level. The RefleXion system is designed to facilitate delivery of biology-guided 
radiotherapy (BgRT). The system uses PET emissions to guide radiotherapy delivery in real-time and 
has been studied for use with FDG. In the future, BgRT guided by [18F]-DCFPyL as a biological fiducial 
carries a potential to improve radiotherapy dose distribution for patients with prostate cancer.  
As a requirement for such future evaluation of [18F]-DCFPyL as a biological fiducial, an understanding 
of the performance of the PET imaging subsystem on the RMRS is needed to correctly detect PET signals 
derived from [18F]-DCFPyL. Therefore, a single-arm, prospective study to better assess and possibly 
optimize the performance of the PET imaging subsystem for detection of [18F]-DCFPyL PET signals as 
a foundation to evaluate [18F]-DCFPyL-based BgRT treatment planning and delivery in future studies is 
being proposed.  
On the day of, and upon completing SOC [18F]-DCFPyL PET-CT, patients will undergo an additional 
“imaging-only session” on the RefleXion PET-CT (Figure 1). Aside from standard of care (SOC) [18F]-
DCFPyL, no PET tracer or other molecule will be administered, and no external-beam radiotherapy will 
be delivered in this study.  
Evidence to be gathered in this study is intended to allow assessment of the technical performance of 
the PET imaging subsystem on RMRS in patients with prostate cancer undergoing SOC imaging with 
[18F]-DCFPyL for diagnostic purposes. Evidence from this study will supplement and enhance technical 
understanding of the [18F]-DCFPyL-guided BgRT delivery. As such, the patient population selected for 
this investigation is meant to optimally represent the spectrum of cases, with respect to motion and 
radiographic environment that a radiation oncologist may encounter in practice.  
 
Protocol Title 
A Prospective Study of the RefleXion [18F]- DCFPyL PET-CT Subsystem Imaging Performance in 
Patients with Prostate Cancer 
Study Detail 
Population/Indication(s): 
Patients with prostate cancer who will be undergoing ([18F]-DCFPyL) PET-
CT scan 
Phase: 
pilot 
Sample Size: 
25 evaluable patients 
Estimated Accrual Duration: 
18 months 
Estimated Study Duration 
24 months 
Participant Duration: 
72 hours 
Study Agents: 
NA 
 
 
 
 

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Study Design 
Single arm, prospective study 
Objectives 
Primary Objective(s) 
 To determine the imaging performance of 2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine-3-carbonyl)-amino]-
pentyl}-ureido)-pentanedioic acid ([18F]-DCFPyL) PET-CT imaging subsystem of the RefleXion Medical 
Radiotherapy System Device in patients undergoing standard-of-care (SOC) [18F]-DCFPyL PET-CT on the 
same day. 
Endpoints 
Primary Endpoint(s): 
 To compare imaging performance of the [18F]-DCFPyL PET-CT subsystem on the X1 RMRS to detect lesions 
(primary and metastatic) in patients with prostate cancer, relative to diagnostic [18F]-DCFPyL PET-CT.  
Secondary Endpoint(s):  
 Percent of cases where X1 RMRS PET data can be used to generate an acceptable BgRT plan such that 
dosimetric parameters for the target and the nearby normal anatomy are met based on investigator 
assessment. 
Intervention Description 
Baseline Assessments within thirty days prior to the X1 RMRS PET Imaging-only session: 
• 
Demographics & medical history 
• 
SOC diagnostic [18F]-DCFPyL PET-CT  
• Subject weight and height 
• Injected dose and injection time of [18F]-DCFPyL 
• Scan time and image analysis of SOC PET-CT  
 
X1 PET Imaging-only session 
• 
Scan time and image analysis of X1 RMRS imaging-only session 
 
Follow-Up  
• 
Comparison of SOC  PET-CT and X1 with respect to image analysis and treatment planning 
• 
Within 72 hours of completion of X1 PET Imaging-only session: Adverse Events assessment by using 
Common Terminology Criteria for Adverse Events (CTCAE) v5 
Main Eligibility Criteria 
Main Inclusion Criteria 
 Age 21 years or greater 
 Able and agree to provide informed consent  
 Patients with prostate cancer undergoing SOC [18F]-DCFPyL PET-CT.  
Main Exclusion Criteria 
 Known psychiatric or substance abuse disorder that would interfere with conduct of the study 
 Patient weight exceeding the weight limit (450 pounds) outlined per X1 RMRS specifications sheet. 
 
 

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TABLE OF CONTENTS 
SECTION…………………………………………………………………………………………………………………PAGE 
Protocol Team ............................................................................................................................................................ 2 
Study Schema ............................................................................................................................................................ 3 
Protocol Synopsis ....................................................................................................................................................... 4 
Table of Contents ....................................................................................................................................................... 6 
Abbreviations .............................................................................................................................................................. 8 
1.0 
Objectives ...................................................................................................................................................... 9 
1.1 
Primary Objective(s) 
9 
1.2 
Secondary Objective(s 
9 
2.0 
Background .................................................................................................................................................... 9 
2.1 
Overview and Justification for Study Design 
9 
3.0 
Eligibility Criteria .......................................................................................................................................... 11 
3.1 
Inclusion Criteria 
11 
3.2 
Exclusion Criteria 
11 
4.0 
Participant Enrollment, Assignment............................................................................................................. 12 
4.1 
Pre-Enrollment Informed Consent and Screening Procedures 
12 
4.2 
Participant Enrollment 
12 
4.3 
Screen Failures and Registered Participants Who Do Not begin Study Intervention 
12 
5.0 
STUDY Program .......................................................................................................................................... 12 
5.1 
Study Plan 
12 
5.2 
Duration of Study 
13 
5.3 
Duration of Study Participation 
13 
5.4 
Sources of Methods of Recruitment 
13 
6.0 
Anticipated Adverse Events ......................................................................................................................... 13 
7.0 
STUDY CALENDAR .................................................................................................................................... 14 
8.0 
Endpoint Definitions/Measurement of Effect ............................................................................................... 14 
8.1 
Primary Endpoint 
14 
8.2 
Secondary Endpoint(s) 
14 
9.0 
Statistical Considerations ............................................................................................................................ 14 
9.1 
Study Analysis/Statistics 
14 
9.2 
Participant Evaluability and Replacement 
15 
9.3 
Sample Size, Accrual Rate and Study Duration 
15 
10.0 
Data Handling, Data Management, Record Keeping .................................................................................. 15 
10.1 
Source Documents 
15 
10.2 
Data Capture Methods and Management 
15 
10.3 
Case Report Forms/Data Submission Schedule 
16 
10.4 
Regulatory Records 
16 
11.0 
Reporting of Adverse Events, Unanticipated Problems & Other Events of Interest .................................... 17 
11.1 
Assessment of Adverse Events 
17 
11.2 
Expedited Reporting 
17 
11.3 
Reporting to Industry Partners 
Error! Bookmark not defined. 
12.0 
Adherence to the Protocol & Reporting of Protocol Deviations ................................................................... 18 
12.1 
Reporting by COH 
Error! Bookmark not defined. 
13.0 
Study Oversight, Quality Assurance, & Data and Safety Monitoring .......................................................... 19 
13.1 
All Investigator Responsibilities 
19 
13.2 
Study Principal Investigator Responsibilities 
19 
13.3 
Protocol Management Team (PMT) 
19 
13.4 
Risk Determination 
19 
13.5 
City of Hope Data and Safety Monitoring Committee 
Error! Bookmark not defined. 

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14.0 
Ethical and Regulatory Considerations ....................................................................................................... 20 
14.1 
Ethical Standard 
20 
14.2 
Regulatory Compliance 
20 
14.3 
Institutional Review Board 
20 
14.4 
Informed Consent 
20 
14.5 
Participant Withdrawal 
21 
14.6 
Special and Vulnerable Populations 
21 
14.7 
Participant Confidentiality 
22 
14.8 
Conflict of Interest 
22 
14.9 
Financial Obligations, Compensation, and Reimbursement of Participants 
22 
14.10 
Publication/ Data Sharing 
23 
15.0 
References .................................................................................................................................................. 23 
 
 
 
 

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ABBREVIATIONS  
 
Abbreviation 
Meaning 
AE 
Adverse Event 
CFR 
Code of Federal Regulations 
COH 
City of Hope 
CR 
Complete Response 
CRC 
Clinical Research Coordinator 
CRF 
Case Report Form 
CTCAE 
Common Terminology Criteria for Adverse Events 
DCC 
Data Coordinating Center 
DLT 
Dose Limiting Toxicity 
DSMC 
Data & Safety Monitoring Committee 
DSMP 
Data & Safety Monitoring Plan 
EOT 
End of Treatment 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HIV 
Human Immunodeficiency Virus 
IB 
Investigator’s Brochure 
IDS 
Investigational Drug Services 
IND 
Investigational New Drug 
IRB 
Institutional Review Board 
MTD 
Maximum Tolerated Dose 
NCI 
National Cancer Institute 
NIH 
National Institutes of Health 
OCTM  
Office of Clinical Trials Monitoring 
OIDRA 
Office of IND Development and Regulatory Affairs 
PD 
Progressive Disease 
PI 
Principal Investigator 
PMT 
Protocol Management Team 
PR 
Partial Response 
RP2D 
Recommended Phase 2 Dose 
SAE 
Serious Adverse Event 
SD 
Stable disease 
UT 
Unacceptable Toxicity 
 

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1.0 OBJECTIVES 
1.1 Primary Objective(s)  
o To assess imaging performance of the [18F]-DCFPyL PET-CT subsystem on the X1 RMRS to 
detect lesions (primary and metastatic) in patients with prostate cancer. 
1.2 Secondary Objective(s) 
o To determine the feasibility of generating a BgRT plan using X1 RMRS-acquired [18F]-DCFPyL 
PET data derived from the imaging-only session at the studied dose level. 
2.0 BACKGROUND 
2.1 Overview and Justification for Study Design 
2.1.1 [18-F]-DCFPyL PET-CT 
Prostate-specific membrane antigen (PSMA) PET with 2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine-3-
carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid ([18F]-DCFPyL) has been approved for imaging 
PSMA positive lesions in men with prostate cancer with either primary high-risk prostate cancer with 
suspected metastasis who are candidates for initial definitive therapy or suspected recurrence based on 
elevated serum prostate-specific antigen (PSA) level (1).  
This approval was based on findings from the CONDOR (2) and OSPREY (3) studies. The multicenter 
phase 3 CONDOR study included 208 men with biochemical recurrence, defined as rising PSA ≥0.2 
ng/mL after prostatectomy or ≥2 ng/mL above nadir after radiation therapy. A total of 63.9% of patients 
who had no evidence of disease on conventional imaging had a change in management after [18F]-
DCFPyL PET-CT was performed. The disease detection rate was 59% to 66% (at least one lesion 
detected per patient by [18F]-DCFPyL PET-CT) (2). In the phase 2/3 OSPREY trial, [18F]-DCFPyL PET-
CT was assessed in two patient cohorts. Cohort A included men with high-risk prostate cancer 
undergoing surgery, and the researchers assessed the capacity of [18F]-DCFPyL PET-CT to detect 
prostate cancer in pelvic lymph nodes. Cohort B included patients with suspected metastatic or recurrent 
disease, and the researchers examined the performance of [18F]-DCFPyL PET-CT in detecting distant 
metastases. In cohort A, [18F]-DCFPyL PET-CT detected in the pelvic lymph nodes with a specificity of 
97.9%, a sensitivity of 40.3%, and a positive predictive value (PPV) of 86.7%. The sensitivity and PPV 
rates for detecting metastatic lesions in cohort B were 95.8% and 81.9%, respectively (3). In the OSPREY 
and CONDOR studies, [18F]-DCFPyL PET-CT was found to be safe and well tolerated (2,3). Another 
study (4) evaluated 160 patients with high-risk prostate cancer. 56% of the included patients were shown 
to have metastatic disease based on [18F]-DCFPyL PET-CT, and 17% of patients had a change in 
management based on the PET-CT findings. Only 1% of patients had to undergo additional imaging 
because of equivocal findings on the [18F]-DCFPyL PET-CT. Authors concluded that [18F]-DCFPyL 
PET-CT should be used as first-line imaging modality for therapy selection in patients with primary high-
risk prostate cancer. 
2.1.2 RefleXion Medical Radiotherapy System and biology-guided radiotherapy 
The RefleXion Medical Radiotherapy System (RMRS) is a hybrid imaging-therapy system that is FDA 
cleared (K190978) to deliver IMRT/SBRT/SRS external beam radiation therapy. It consists of 6 
megavoltage (MV) photon radiotherapy delivery, PET imaging hardware, kilovoltage (kV) X-ray CT 
imaging, and treatment planning subsystems. The system includes the capability of PET imaging when 
used in a research mode. 
 

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It is hypothesized that BgRT guided by [18F]-DCFPyL as a biological fiducial may improve radiotherapy 
dose distribution for patients with prostate cancer. As a requirement for such evaluation of [18F]-DCFPyL 
as a biological fiducial, the performance of the PET imaging subsystem on the X1 RMRS to correctly 
detect PET signals derived from [18F]-DCFPyL, needs to be better understood. Therefore, a single-arm, 
prospective study to better assess and possibly optimize the performance of the PET imaging subsystem 
for detection of [18F]-DCFPyL PET signals as a foundation to evaluate [18F]-DCFPyL-based BgRT 
treatment planning and delivery in subsequent studies, is proposed.  
On the day of, and upon completing the standard of care (SOC) [18F]-DCFPyL PET-CT, patients will 
undergo an addition “imaging-only session” on the X1 RMRS PET-CT (Figure 1). No additional PET 
tracer or any other molecule will be administered, and no therapeutic radiation will be delivered in this 
study. 
The evidence to be gathered in this study is intended to allow assessment of the technical performance 
of the PET imaging subsystem on the X1 in a clinically relevant situation, namely in patients with prostate 
cancer undergoing SOC imaging with [18F]-DCFPyL. Long term, the evidence from this study will 
supplement and enhance technical understanding of the [18F]-DCFPyL-guided BgRT delivery. As such, 
the patient population selected for this investigation is meant to optimally represent the spectrum of 
cases, with respect to motion and radiographic environment, that a radiation oncologist may encounter 
in practice.  
 
 
Figure 1: Study Flowchart 

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3.0 ELIGIBILITY CRITERIA 
 
Patient MRN (COH Only) 
Patient Initials (F, M, L): 
Participants must meet all of the following criteria on screening examination to be eligible to participate 
in the study:  
3.1 Inclusion Criteria 
 
__1. Documented informed consent of the participant and/or legally authorized representative. 
__2. Age: ≥ 21 years 
__3. Patients undergoing SOC [18F]-DCFPyL PET-CT  
__4. Patients should be scheduled for [18F]-DCFPyL PET-CT prior to study entry 
 
3.2 Exclusion Criteria 
 
__1.  Known psychiatric or substance abuse disorder that would interfere with conduct of the study 
__2.  Patient weight exceeding the weight limit (450 pounds) outlined per X1 RMRS specifications sheet. 
 
Eligibility Confirmed* 
by 
(Choose 
as 
applicable): 
Print Name 
Signature 
Date 
 Site PI 
 
 
 
 Authorized study 
MD 
 
 
 
 Study Nurse 
 
 
 
 Study CRA/ CRC 
 
 
 
Other:_____________
_ 
 
 
 
*Eligibility should be confirmed per institutional policies. 
 
 

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4.0 PARTICIPANT ENROLLMENT, ASSIGNMENT  
4.1 Pre-Enrollment Informed Consent and Screening Procedures 
The informed consent process is to be fully documented (see Section 13.4), and the prospective 
participant must receive a copy of the signed informed consent document. Screening procedures are 
listed in Section 7.0 (Study Calendar). 
4.2 Participant Enrollment 
Registration of participants will be according to the following steps: 
o Prospective participants must complete the informed consent process, including a signed 
informed consent, prior to proceeding to study screening. 
o Once all the pre-study requirements have been fulfilled, including a completed eligibility checklist 
(Section 3.0) the study coordinator will register the eligible patient into the OnCore Clinical Trials 
Management System. 
o Patients failing to meet all protocol eligibility criteria, including informed consent, may not be 
registered for the trial. 
4.3 Screen Failures and Registered Participants Who Do Not begin Study Intervention 
Notify the study team immediately if the participant screen fails after registration or if the participant does 
not start intervention. 
5.0 STUDY PROGRAM 
5.1 Study Plan 
SOC [18F]-DCFPyL PET-CT 
All SOC [18F]-DCFPyL PET-CT studies should be performed on the Siemens Vision 600 PET-CT 
machine in the Outpatient Imaging Center (OIC) in the Department of Nuclear Medicine at City of Hope, 
in accordance with departmental protocol. Patients who demonstrate at least one PET avid site will then 
have a PET-CT on the RefleXion X1 system. A PET avid site could include the prostate gland or a 
metastatic site. If no PET avid lesion is seen on the SOC [18F]-DCFPyL PET-CT, then the patient will 
not have a PET-CT on the RefleXion X1 system.  
Imaging-only session on the RefleXion X1 machine 
On the day of, and upon completing the standard of care (SOC) [18F]-DCFPyL PET-CT, patients will 
undergo an addition “imaging-only session” on the RefleXion PET-CT. Site should make every effort to 
start SOC [18F]-DCFPyL PET-CT scan within 60 minutes of SOC [18F]-DCFPyL injection and 
subsequently start X1 RMRS scan within 120 minutes post injection (Figure 1). No additional PET tracer 
or any other molecule will be administered, and no therapeutic radiation will be delivered in this study. 
See Appendix for additional details of workflow.  
 
Post-image-acquisition transfer of anonymized image data to the Funding Support/Industry Partner will 
be within one week from the X1 PET scan.  
 
BgRT Planning 

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Within a week after the X1 RMRS PET scan a BgRT plan will be generated using X1 RMRS-acquired 
[18F]-DCFPyL PET data derived from the imaging-only session. The percent of cases where X1 RMRS 
[18F]-DCFPyLPET data can be used to generate an acceptable BgRT plan such that dosimetric 
parameters for the target and the nearby normal anatomy are met based on investigator assessment will 
be determined. 
5.2 Duration of Study 
Enrollment is estimated to occur over  twelve to eighteen (12-18) months, and for the total study duration 
to be approximately eighteen to twenty-four(18-24) months.  
5.3 Duration of Study Participation 
Study patients can expect to be participants of this study for no longer than 72 hours. Both imaging 
sessions (SOC [18F]-DCFPyL PET-CT and imaging on X1 RMRS) will take place on the same day, and 
adverse events assessment will take place within 72 hours after the imaging session. 
5.3.1 Withdrawal and Replacement of Subjects 
Subjects may withdraw their consent at any time. Subject’s withdrawal of consent must be documented. 
Withdrawn subjects will not undergo any additional follow-up. Patients with imaging results deemed 
unevaluable will be replaced. 
5.4 Sources of Methods of Recruitment 
Patients will be recruited from those seen at the Department of Radiation Oncology at City of Hope. After 
eligibility criteria have been reviewed, eligible patients will be offered the opportunity to participate in the 
study. A brief description of the study will be given verbally to the patients, followed by written informed 
consent, and any relevant supplemental material as needed. The patients will be given ample time to 
review the consent and a time for questions and answers will be provided. No financial incentives will be 
provided to the patients. 
6.0 ANTICIPATED ADVERSE EVENTS 
Subjects will undergo localization (positioning) scans with the X1 RMRS integrated fan-beam kVCT 
imaging prior to the PET image collection session. Effectively, the only extra dose (on top of SOC [18F]-
DCFPyL PET-CT scan) will be coming from this kVCT. A significant increase in subjects’ risk with this 
additional imaging session is not expected. For a single additional kVCT scan with the X1 RMRS, the 
extra effective dose a patient could receive usually ranges between 10-15 mSv, or 1.0-1.5 cGy.  Based 
on the established clinical literature (5,6,7), the degree of risk for populations of this additional low dose 
is unclear and controversial, but the risk for any one individual is remote. Study subjects will continue to 
receive standard of care treatments throughout the study, which are not part of these study procedures.  
Appropriate clinical assessments will be performed as indicated to identify all AEs. AEs will be graded 
according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5. Signs and 
symptoms of existing disease progression will not be considered AEs. 
 

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7.0 STUDY CALENDAR 
Assessments 
Baseline* 
Day 0 
Follow-up^ 
Informed Consent 
X 
 
 
Demographics 
X 
 
 
Medical History 
X 
 
 
Height/Weight 
X 
 
 
SOC [18F]-DCFPyL 
PET-CT 
 
X 
 
X1 PET Imaging-only 
session 
 
X 
 
Toxicity Collection 
 
 
X 
*Within thirty days prior to the X1 PET Imaging-only session: 
^Within 72 hours of completion of X1 RMRS PET Imaging-only session: Adverse Events assessment by using 
Common Terminology Criteria for Adverse Events (CTCAE) v5 
8.0 ENDPOINT DEFINITIONS/MEASUREMENT OF EFFECT 
8.1 Primary Endpoint  
To compare imaging performance of the [18F]-DCFPyL PET-CT subsystem on the X1 RMRS to detect 
lesions (primary and metastatic) in patients with prostate cancer with the diagnostic [18F]-DCFPyL PET-
CT. 
8.2 Secondary Endpoint(s) 
Percent of cases where X1 RMRS [18F]-DCFPyLPET data can be used to generate an acceptable BgRT 
plan such that dosimetric parameters for the target and the nearby normal anatomy are met based on 
investigator assessment. 
9.0 STATISTICAL CONSIDERATIONS 
9.1 Study Analysis/Statistics 
This study will compare the performance of the [18F]-DCFPyL PET-CT subsystem on the RefleXion X1 
system to detect selected lesions in patients with prostate cancer with the SOC diagnostic [18F]-DCFPyL 
PET-CT.  
One key metric will be the percent of patients with lesions identified on SOC PET-CT that are not identified 
on X1 (false negatives if considering SOC the true standard).  While patients will not have their SOC scan 
evaluated prior to X1, we anticipate at least 50% will have positive lesions identified on SOC in our patient 
population.  With 12 patients with SOC detected lesions, there is at least 14% chance of finding a false 
negative if the true false negative rate is 15%, and 93% of observing a false negative if the true false 
negative rate is 20%.   
 For the SOC [18F]-DCFPyL PET-CT, the maximum SUV and the greatest dimension in centimeters will 
be recorded for each PET avid malignant lesion identified by the nuclear medicine radiologist. The 

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patient’s radiation oncologist will interpret the X1 PET scan for the same metrics. Any discordances will 
be documented, and the final disposition recorded after a discussion between the radiation oncologist 
and the nuclear medicine radiologist.  
Graphical presentations will be provided to compare SOC positive lesions and X1 positive lesions, and 
SOC positive lesions and X1 negative lesions with regards to lesion size, lesion location (bone, lymph 
nodes, soft tissue, visceral organ) and SUV uptake. 
The true positive lesions identified on the X1 PET images will be identified and used for BgRT planning.  
For the secondary endpoint, simulated planning using the RefleXion treatment planning software will be 
performed, and the radiation dose to organs at risk calculated. Principal investigator will determine 
whether this plan is acceptable or not. The percent of cases in which RefleXion [18F]-DCFPyLcPET data 
led to an acceptable plan will be recorded (descriptive statistics). 
Because this is an exploratory study, descriptive statistics will be utilized to quantify results. Mean, 
standard deviation, IQR, and range will be reported for each continuous variable. Frequency and 
percentage will be reported for categorical variables. Statistical significance will be assessed at the 0.05 
level, one-sided. 
9.2 Participant Evaluability and Replacement 
Patients with imaging results deemed unevaluable will be replaced. 
9.3 Sample Size, Accrual Rate and Study Duration  
o Total accrual: We will accrue a maximum of 25 evaluable participants  
o Accrual rate: Accrual is expected to be completed in 12 months. 
o Study duration is expected to be about 18 months. 
o Participant duration will be about 72 hours 
This study is designed to enroll up to 25 evaluable patients, and criteria for patient selection are outlined 
above.  This sample size was determined a priori to represent a sufficient number of patients for a pilot 
study to evaluate PSMA-positive lesions to describe imaging performance of the [18F]-DCFPyL PET-CT 
subsystem on the RefleXion X1 system across a spectrum of clinical scenarios. 
10.0 DATA HANDLING, DATA MANAGEMENT, RECORD KEEPING 
10.1 Source Documents 
Source documents are original documents, data, and records (e.g., medical records, pharmacy 
dispensing records, recorded data from automated instruments, laboratory data) that are relevant to the 
clinical trial. The Investigator or their designee will prepare and maintain adequate and accurate source 
documents. These documents are designed to record all observations and other pertinent data for each 
patient enrolled in this clinical trial. Source documents must be adequate to reconstruct all data 
transcribed onto the case report forms. 
10.2 Data Capture Methods and Management 
Data for this trial will be collected using City of Hope’s electronic capture system (EDC) that is compliant 
with 21 CFR Part 11.  
Study personnel will enter data from source documents corresponding to a subject’s visit into the protocol-
specific electronic Case Report Form (eCRF).   

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10.3 Case Report Forms/Data Submission Schedule 
The Investigator is responsible for all information collected on subjects enrolled in this study. All data 
collected during the course of this study must be reviewed and verified for completeness and accuracy 
by the Investigator. All case report forms must be completed by designated study personnel. The 
completed case report forms must be reviewed, signed and dated by the Investigator or designee in a 
timely fashion. 
All data will be collected using electronic data collection, stored as indicated in Section 13.2, and will be 
submitted according to the timelines indicated below. 
Data to be collected will include patient’s name and medical record number, date of birth, basic disease 
characteristics, including staging information, location of and extent of involvement, relevant imaging 
characteristics of the tumor, prior cancer-directed therapies. [18F]-DCFPyL emission data will be 
collected at time of study acquisition in the Department of Nuclear Medicine. The images sets and [18F]-
DCFPyL activity data is stored on a picture archiving and communication system (PACS) per protocol 
and submitted securely to the appropriate members of the Industry Partner’s study team, along with 
deidentified clinical data. City of Hope approved case report forms (CRFs) for data collection will be used 
and data entered into a secure electronic data capture (EDC) system. City of Hope will share the raw 
EDC data with Industry Partner.  Every reasonable effort should be made to complete data entry within 
five business days of data collection. The Principal Investigator or Sub-investigator must ensure the 
accuracy and completeness of the recorded data and then provide his/her electronic signature on the 
appropriate CRFs.  
Baseline Assessments within thirty days prior to the X1 PET Imaging-only session: 
• 
Demographics & medical history 
• 
Subject weight and height 
• 
Injected dose and injection time of [18F]-DCFPyL 
• 
Scan time of SOC [18F]-DCFPyL PET-CT  
X1 PET Imaging-only session 
• 
Scan time of X1 RMRS imaging-only session 
Follow-Up  
• 
Within 72 hours of completion of X1 RMRS PET Imaging-only session: Adverse Events 
assessment by using Common Terminology Criteria for Adverse Events (CTCAE) v5 
 
10.4 Regulatory Records 
The Investigator will maintain regulatory records, including updating records in accordance with Good 
Clinical Practice guidelines and FDA regulations. 

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11.0 ADVERSE EVENTS AND UNANTICIPATED PROBLEMS 
The research team is responsible for classifying adverse events (AEs) and unanticipated problems (UPs) 
as defined in the relevant regulations and reporting to all applicable parties, including but not limited to 
the COH IRB, DSMC, Food and Drug Administration (FDA), National Institutes of Health (NIH) and other 
collaborators, e.g., pharmaceutical companies. The research team is responsible for the continued 
monitoring and tracking of all AEs in order to ensure non-reportable events are reviewed and monitored 
and do not rise to a reporting level. 
11.1 Assessment of Adverse Events 
The site Investigator will be responsible for determining the event name, and assessing the severity (i.e., 
grade), expectedness, and attribution of all adverse events as applicable per the City of Hope Clinical 
Research Adverse Event and Unanticipated Problem policy. Adverse events will be characterized using 
the descriptions and grading scales found in NCI CTCAE v5.0. A copy of the scale can be found at: 
https://ctep.cancer.gov/protocoldevelopment/electronic_applications/ctc.htm.  
The following definitions will be used to determine the causality (attribution) of the event to the study 
agent or study procedure. 
o Unrelated – The event is clearly NOT related to study procedure, and is clearly related to other 
factors such as the participant’s clinical state, other therapeutic interventions, or concomitant 
medications administered to the participant. 
o Unlikely – The event is unlikely related to the study procedure, and is most likely related to other 
factors such as the participant’s clinical state, other therapeutic interventions, or concomitant 
drugs. 
o Possible – The event may be related to study procedure, as it follows a reasonable temporal 
sequence from the time of study procedure, but could have been produced by other factors such 
as the participant’s clinical state, other therapeutic interventions, or concomitant drugs.  
o Probable – The event is most likely related to the study procedure, as it follows a reasonable 
temporal sequence from the time of study procedure and a known response pattern to the study 
procedure, and is unlikely related to the participant’s clinical state, other therapeutic interventions, 
or concomitant drugs.  
o Definite – The event is clearly related to the study procedure, as it follows a reasonable temporal 
sequence from the time of study procedure and a known response pattern to the study procedure, 
and is not reasonably explained by other factors such as the participant’s condition, therapeutic 
interventions, or concomitant drugs.  
11.2 Reporting of Adverse Events 
11.2.1 Routine Recording of Non-Serious Adverse events 
Routine recording of the worst grade of all adverse events will occur via data entry into the study eCRF. Collection 
of adverse events will begin at the beginning of the imaging-only session on the X1 RMRS system and will continue 
until 72 hours after the end of the scan. Adverse events will be monitored by the Protocol Management Team 
(PMT). Adverse events that do not meet the criteria of serious OR are not unanticipated problems do not require 
expedited reporting.  AEs reported through expedited processes (i.e. reported to the IRB, DSMC, FDA, etc.) must 
also be reported in routine study data submissions.  
 

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11.2.2 Expedited Reporting Requirements of SAEs and UPs to the COH Regulatory Committees 
Adverse events that meet the criteria of serious OR are unanticipated problems will be reported according to the 
approved City of Hope Clinical Research Adverse Event and Unanticipated Problem policy. Reporting of SAEs will 
begin at the beginning of the imaging-only session on the X1 RMRS machine through 72 hours post completion of 
the scan, and must be followed until the event is resolved, stabilized, or determined to be irreversible by the 
investigator.  Follow-up SAE reports must be submitted for all events that require expedited reporting when the 
status of the event changes and until the resolution or stabilization of the event.  
 
11.2.3 Reporting to RefleXion 
All serious adverse events and AESIs (initial and follow-up information) will be reported by the study PI to RefleXion 
per the following guidelines:  
 
Type of 
Report 
Reporting Timeframes to Industry 
Partner 
Pregnancy 
Within 48 hours of being aware of the 
event using the protocol case report form. 
All expedited 
SAE reports 
(includes 
AESIs) 
Within 24 hours of being aware of the 
event via a MedWatch 3500A form. 
 
Aggregate 
safety reports  
Forward to Industry Partner every 6 
months (e.g. at time of COH PMT report). 
 
 
12.0 PROTOCOL DEVIATIONS 
Deviations from the protocol should be avoided, except when necessary to eliminate immediate hazard(s) 
for the protection, safety, and well-being of a research participant. As a result of deviations, corrective 
actions are to be developed by the study staff and implemented promptly. All protocol deviations and 
planned protocol deviations will be reported in accordance with the Clinical Research Protocol Deviation 
policy. In addition, if contractually obligated, the industry partner/funding source must also approve 
planned deviations, as necessary. 

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13.0 STUDY OVERSIGHT, QUALITY ASSURANCE, & DATA AND SAFETY MONITORING 
13.1 All Investigator Responsibilities 
An investigator is responsible for ensuring that an investigation is conducted according to the signed 
investigator statement, the investigational plan, and applicable regulations; for protecting the rights, 
safety, and welfare of subjects under the investigator's care; and for the control of drugs under 
investigation.  
13.2 Study Principal Investigator Responsibilities 
The Study Principal Investigator is responsible for the conduct of the clinical trial, including overseeing 
that sponsor responsibilities are executed in accordance with federal regulations.  
13.3 Protocol Management Team (PMT) 
The Protocol Management Team (PMT), minimally consisting of the study PI, collaborating investigators,  
research nurse, clinical research associate/coordinator, and the study biostatistician, is responsible for 
ongoing monitoring of the data and safety of this study, including implementation of the stopping rules for 
safety/toxicity. 
The PMT is recommended to meet (in person or via teleconference) to review study status. The meeting 
is a forum to discuss study related issues including accrual, SAE/AE/UPs experienced, study response, 
deviations/violations, and study management issues. The appropriateness of further subject enrollment 
and the specific intervention for subsequent subject enrollment are addressed.  
13.4 Quality Assurance 
Clinical site auditing is conducted to ensure that the rights of human subjects are protected, that the study 
is implemented in accordance with the protocol and regulatory requirements, and that the quality and 
integrity of study data and data collection methods are maintained.  This trial will be audited by the City 
of Hope Office for Safety and Data Quality. Details of clinical site auditing are documented in the City of 
Hope Institutional Data and Safety Monitoring Plan (DSMP).  
13.5 Risk Determination  
This is a low risk study, as defined in the City of Hope Institutional Data and Safety Monitoring Plan 
(DSMP). This determination was made because the study is an investigator initiated study and because 
it involves only an additional scan with no additional infusion of tracer agents nor radiotherapy. This study 
also satisfies the definition of a Nonsignificant Risk Medical Device Study as defined by the FDA. 
13.6 City of Hope Data and Safety Monitoring Committee 
The COH Data and Safety Monitoring Committee (DSMC) will review and monitor study progress, 
compliance, toxicity, safety, and accrual data from this trial via the PMT Progress Report (submitted by 
the Study Principal Investigator according to the frequency outlined in the City of Hope Institutional 
DSMP). The DSMC is composed of clinical specialists who have no direct relationship with the study. 
Information that raises any questions about participant safety will be addressed with the Protocol 
Management Team.  

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14.0 ETHICAL AND REGULATORY CONSIDERATIONS 
14.1 Ethical Standard 
This study will be conducted in conformance with the principles set forth in The Belmont Report: Ethical 
Principles and Guidelines for the Protection of Human Subjects of Research (US National Commission 
for the Protection of Human Subjects of Biomedical and Behavioral Research, April 18, 1979) and the 
Declaration of Helsinki. 
14.2 Regulatory Compliance 
This study is to be conducted in compliance with the IRB approved protocol and according to the following 
considerations: 
o US Code of Federal Regulations (CFR) governing clinical study conduct 
 Title 21 Part 11 – Electronic Records; Electronic Signatures  
 Title 21 Part 50 – Protection of Human Subjects  
 Title 21 Part 54 – Financial Disclosure by Clinical Investigators  
 Title 21 Part 56 – Institutional Review Boards  
 Title 21 Part 58 – Good Laboratory Practice for Nonclinical Laboratory Studies  
 Title 45 Part 46 – Protection of Human Subjects  
o US Federal legislation, including but not limited to 
 Health Insurance Portability and Accountability Act of 1996  
 Section 801 of the Food and Drug Administration Amendments Act   
o Applicable state and local laws. For research occurring in California, this includes but is not limited 
to State of California Health and Safety Code, Title 17 
o Applicable institutional research policies and procedures 
14.3 Institutional Review Board 
An Institutional Review Board (IRB) that complies with the federal regulations at 45 CFR 46 and 21 CFR 
50, 56 and State of California Health and Safety code, Title 17, must review and approve this protocol, 
informed consent form and any additional documents that the IRB may need to fulfill its responsibilities 
(Investigator’s Brochure, information concerning patient recruitment, payment or compensation 
procedures, or other pertinent information) prior to initiation of the study. Revisions to approved 
documents will require review and approval by the IRB before the changes are implemented in the study. 
All institutional, Federal, and State of California regulations must be fulfilled. 
The IRB’s written unconditional approval of the study protocol and the informed consent document must 
be in the possession of the investigator before the study is initiated. 
The IRB will be informed of serious unexpected, unanticipated adverse experiences, and unanticipated 
problems occurring during the study, and any additional adverse experiences in accordance with the 
standard operating procedures and policies of the IRB; new information that may affect adversely the 
safety of the patients of the conduct of the study; an annual update and/or request for re-approval; and 
when the study has been completed. 
14.4 Informed Consent 
The Principal Investigator or IRB approved named designee will explain the nature, duration, purpose of 
the study, potential risks, alternatives and potential benefits, and all other information contained in the 
informed consent document. In addition, they will review the experimental subject’s bill of rights if 
applicable, and the HIPAA research authorization form. Prospective participants will be informed that 
they may withdraw from the study at any time and for any reason without prejudice, including as 
applicable, their current or future care or employment at City of Hope or any relationship they have with 

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City of Hope. Prospective participants will be afforded sufficient time to consider whether or not to 
participate in the research. 
After the study has been fully explained, written informed consent will be obtained from either the 
prospective participant or his/her guardian or legal representative before study participation. The method 
of obtaining and documenting the informed consent and the contents of the consent must comply with 
the ICH-GCP and all applicable regulatory requirements. 
A copy of the signed informed consent will be given to the participant or his/her legally authorized 
representative. The original signed consent must be maintained by the investigator and available for 
inspection by Industry Partner designated representatives, or regulatory authority at any time. 
Informed consent is a process that is initiated prior to the individual agreeing to participate in the study 
and continues throughout study participation. 
14.5 Participant Withdrawal 
Participants may withdraw from the study at any time and for any reason without prejudice. The 
withdrawal must be documented per institutional policies.  
Participant withdrawal may consist of any of the following with regard to study procedures and data 
collection: 
o Withdrawal from study treatment, but agreement to continue with active study procedures and 
chart review and survival follow-up. 
o Withdrawal from study treatment and all active procedures, but agreement for chart review and 
survival follow-up. 
o Withdrawal from study treatment, all active procedures, and any future data collection. 
14.6 Special and Vulnerable Populations 
14.6.1 Women and Minorities and Other Underrepresented Populations 
The study is open to anyone regardless of race or ethnicity. Efforts will be made to extend the accrual to 
a representative population impacted by the disease under study and among populations with the City of 
Hope catchment area. If differences in outcome that correlate to racial, or ethnic identity are noted, 
accrual may be expanded or additional studies may be performed to investigate those differences more 
fully.   
14.6.2 Pediatric Population 
Pediatric participants (< 18 years of age) are excluded from this study because the incidence of prostate 
cancer is rare in the pediatric population. 
14.6.3 HIV Positive Individuals 
Participants with HIV are included if eligible based on inclusion criteria. 
14.6.4 Vulnerable Populations 
Per 45 CFR §46.111 (a)(3) and 45 CFR §46, Subparts B-D identifies children, prisoners, pregnant 
women, mentally incapacitated persons, and economically or educationally disadvantaged persons as 
vulnerable populations.  
Adults lacking capacity to consent are not excluded from participation. This study does not pose 
additional risks for adults lacking capacity than for the general population. In such instances, informed 

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consent will be sought and documented from the prospective participant’s legally authorized 
representative in agreement with institutional policies and local IRB approval. 
Economically/educationally disadvantaged persons are not actively targeted for participation, nor are 
they excluded from participation. This study does not pose additional risks for economically/educationally 
disadvantaged persons than for the general population. 
14.7 Participant Confidentiality 
Participant confidentiality is strictly held in trust by the investigators, study staff, and the industry partner 
and their agents. This confidentiality is extended to cover testing of biological samples in addition to any 
study information relating to participants.  
This research will be conducted in compliance with federal and state requirements relating to protected 
health information (PHI), including the requirements of the Health Insurance Portability and Accountability 
Act of 1996 (HIPAA). HIPAA regulations require a signed subject authorization informing the subject of 
the nature of the PHI to be collected, who will have access to that information and why, who will use or 
disclose that information, and the rights of a research participant to revoke their authorization for use of 
their PHI. In the event that a subject revokes authorization to collect or use PHI, the investigator, by 
regulation, retains the ability to use all information collected prior to the revocation of subject 
authorization. For subjects that have revoked authorization to collect or use PHI, attempts should be 
made to obtain permission to collect at least vital status (i.e. that the subject is alive) at the end of their 
scheduled study period. 
Release of research results should preserve the privacy of medical information and must be carried out 
in accordance with Department of Health and Human Services Standards for Privacy of Individually 
Identifiable Health Information, 45 CFR 164.508. When results of this study are reported in medical 
journals or at meetings, identification of those taking part will not be disclosed and no identifiers will be 
used.  
Medical records of subjects will be securely maintained in the strictest confidence, according to current 
legal requirements. Data will be entered, analyzed and stored in encrypted, password protected, secure 
computers that meet all HIPAA requirements. All data capture records, drug accountability records, study 
reports and communications will identify the patient by initials and the assigned patient number.  
The Investigator/Institution will permit direct access to source data and documents by Industry Partner 
representatives, the FDA, and other applicable regulatory authorities. The access may consist of trial-
related monitoring, including remote monitoring, audits, IRB reviews, and FDA/regulatory authority 
inspections. The patient’s confidentiality will be maintained and will not be made publicly available to the 
extent permitted by the applicable laws and regulations. 
14.8 Conflict of Interest 
Any investigator who has a conflict of interest with this study (patent ownership, royalties, or financial 
gain greater than the minimum allowable by their institution, etc.) must have the conflict reviewed by a 
properly constituted Conflict of Interest Committee with a Committee-sanctioned conflict management 
plan that has been reviewed and approved by the study Sponsor (City of Hope) prior to participation in 
this study. All City of Hope investigators will follow the City of Hope conflict of interest policy. 
14.9 Financial Obligations, Compensation, and Reimbursement of Participants 
Neither the research participant nor the insurance carrier will be responsible for the research procedures 
related to this study. 
Standard of care drugs or procedures provided during the course of study participation will be the 
responsibility of the research participant and/or the insurance carrier. The participant will be responsible 

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for all copayments, deductibles, and other costs of treatment and diagnostic procedures as set forth by 
the insurance carrier. The participant and/or the insurance carrier will be billed for the costs of treatment 
and diagnostic procedures in the same way as if the participant were not in a research study.   
In the event of physical injury to a participant resulting from research procedures, appropriate medical 
treatment will be available at City of Hope to the injured participant. There are no plans for City of Hope 
to provide financial compensation in the event of physical injury to a participant.  
The research participant will not receive reimbursement or payment for taking part in this study. 
14.10 Publication/ Data Sharing 
Neither the complete nor any part of the results of the study carried out under this protocol, nor any of 
the information provided by City of Hope for the purposes of performing the study, will be published or 
passed on to any third party without the written approval of the City of Hope PI. Any investigator involved 
with this study is obligated to provide City of Hope with complete test results and all data derived from 
the study. 
The preparation and submittal for publication of manuscripts containing the study results shall be in 
accordance with the process determined by mutual written agreement between City of Hope and Industry 
Partner contained in the Investigator-Initiated Clinical Research Support Agreement between the parties. 
The publication or presentation of any study results shall comply with all applicable privacy laws, 
including, but not limited to, the Health Insurance Portability and Accountability Act of 1996.  
In accordance with the U.S. Public Law 110-85 (Food and Drug Administration Amendments Act of 2007 
or FDAAA), Title VIII, Section 801, this trial will be registered onto ClinicalTrials.gov; it is City of Hope 
policy to register the trial prior to enrollment of the first patient. Results will be reported on 
ClinicalTrials.gov generally within 12 months after the primary completion date unless criteria to delay 
submission are met per the final rule. 
15.0 REFERENCES 
1.  Lantheus Receives U.S. FDA Approval of PYLARIFY® (piflufolastat F 18) Injection, the First 
and Only Commercially Available PSMA PET Imaging Agent for Prostate Cancer. Published 
online May 27, 2021. Accessed Jan 27, 2022. https://bwnews.pr/3vtMgBh. 
2. Morris MJ, Rowe SP, Gorin MA, Saperstein L, Pouliot F, Josephson D, Wong JYC, Pantel AR, 
Cho SY, Gage KL, Piert M, Iagaru A, Pollard JH, Wong V, Jensen J, Lin T, Stambler N, Carroll 
PR, Siegel BA; CONDOR Study Group. Diagnostic Performance of 18F-DCFPyL-PET/CT in 
Men with Biochemically Recurrent Prostate Cancer: Results from the CONDOR Phase III, 
Multicenter Study. Clin Cancer Res. 2021 Jul 1;27(13):3674-3682. doi: 10.1158/1078-
0432.CCR-20-4573. Epub 2021 Feb 23. PMID: 33622706; PMCID: PMC8382991. 
3. Pienta KJ, Gorin MA, Rowe SP, Carroll PR, Pouliot F, Probst S, Saperstein L, Preston MA, Alva 
AS, Patnaik A, Durack JC, Stambler N, Lin T, Jensen J, Wong V, Siegel BA, Morris MJ. A 
Phase 2/3 Prospective Multicenter Study of the Diagnostic Accuracy of Prostate Specific 
Membrane Antigen PET/CT with 18F-DCFPyL in Prostate Cancer Patients (OSPREY). J Urol. 
2021 Jul;206(1):52-61. doi: 10.1097/JU.0000000000001698. Epub 2021 Feb 26. PMID: 
33634707; PMCID: PMC8556578. 
4. Wondergem M, van der Zant FM, Broos WAM, Roeleveld TA, Donker R, Ten Oever D, Geenen 
RWF, Knol RJJ. 18F-DCFPyL PET/CT for primary staging in 160 high-risk prostate cancer 
patients; metastasis detection rate, influence on clinical management and preliminary results of 
treatment efficacy. Eur J Nucl Med Mol Imaging. 2021 Feb;48(2):521-531. doi: 10.1007/s00259-
020-04782-2. Epub 2020 Jul 27. PMID: 32719916. 

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5. Hong J, Han K, Jung J, Kim JS. Association of Exposure to Diagnostic Low-Dose Ionizing 
Radiation With Risk of Cancer Among Youths in South Korea. JAMA Netw 
Open. 2019;2(9):e1910584. doi:10.1001/jamanetworkopen.2019.10584. 
6. Vaiserman A, Koliada A, Zabuga O, Socol Y. Health Impacts of Low-Dose Ionizing Radiation: 
Current Scientific Debates and Regulatory Issues. Dose Response. 
2018;16(3):1559325818796331. Published 2018 Sep 19. doi:10.1177/1559325818796331 
7. Yasser, A. F., Cucinotta, F. A., Ning-Ang, L., Zhou, G. (2020). Cancer Risk of Low Dose 
Ionizing Radiation. Frontiers in Physics, 8 1-9. 
http://dx.doi.org/10.3389/fphy.2020.00234 
 
 
 
 
 
 

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APPENDIX 
 
The following describes the general workflow:  
• For patients who have SOC imaging within 6 weeks prior to SOC [18F]-DCFPyL PET-CT, 
suspicious lesion(s) should be identified prior to [18F]-DCFPyL PET-CT.  
• Upon completion of SOC [18F]-DCFPyL PET-CT, the images are loaded into the contouring system 
(e.g., Eclipse, MIM). 
• The radiation oncologist identifies the lesion(s) on the SOC [18F]-DCFPyL PET-CT to be imaged 
on X1 RMRS. Ideally PET-positive lesions should be between 1-5 cm although PET-positive lesions 
< than 1 cm are acceptable.  
• If no lesion is identified, the patient will be informed that he will not need to undergo imaging on X1 
RMRS. This patient will be non-evaluable for this study. 
• A basic contour of PTV and BTZ is created for each lesion identified. The PTV should be at least 1 
cm in diameter. The BTZ should add 10 mm or more depending on the anticipated amount of target 
motion for each lesion. A dummy OAR is also created. 
 
 
• Load the CT and contour(s) into X1 RMRS. 
• Create an image-only plan with patient reference point (laser confirmation) (to be done by the 
physicist). 
• Safely position the patient onto X1 table, head first, supine: as comfortable and as close to the SOC 
[18F]-DCFPyL PET-CT position as possible. 
• A kVCT localization followed by PET acquisition is then performed on the X1 RMRS. 
• Prioritize pelvic lesion(s) first, before bladder accumulates activity, and low SUV lesions first. 
• Safely remove the patient from the X1 RMRS.  
 
 The estimated time for steps on the X1 RMRS is as follows: 
• 
Loading Patient onto Couch: 5 mins  
• 
Patient Setup: 5 - 10 mins  
• 
Confirming Laser and Move to Scan: 3 mins 
• 
kVCT scan: 3 - 5 mins 
• 
Imaging-only PET scan (depending on scan length): 20 - 35 mins 
• 
Unloading patient from couch: 5 mins 
• 
TOTAL TIME: 40 - 65 mins 

RefleXion [18F]- DCFPyL PET-CT Subsystem Imaging 
City of Hope #:   22189 
Version 01  07/08/2022 
 
 
CONFIDENTIAL 
 
Page 26 
Detailed Timeline 
 
Time 
Point 
(min) 
 
Nuc Med Tech 
CRN 
Rad Onc MD 
Physicists and technologists 
0 
Infuse of pylarify 
 
Notify X1, physicist and rad onc MD   
 
60 
Scan starts 
 
Notify X1, physicist and rad onc MD   
 
90 
Scan ends 
 
Images moved to 
PACS (10-20min) 
Notify X1, physicist and rad onc MD  
 
Transport patient 
 
Scans reviewed and 
lesion(s) selected 
 
Contours added 
 
 
105 
 
Patient arrives in Rad Onc 
 
Load the CT and contour(s) into X1 RMRS.X1 system 
 
Create an image-only plan with patient reference point 
(laser confirmation)  
 
120 
 
 
 
Put patient onto Couch: 5 mins  
 
Patient Setup: 5 - 10 mins  
 
Confirm Laser and Move to Scan: 3 mins 
 
kVCT scan: 3 - 5 mins 
 
Imaging-only PET scan: 20 - 35 mins 
 
Remove patient from couch: 5 mins 
 
TOTAL TIME: 40 - 65 mins 
 
180 
 
 
 
Completed