Strategy to Reduce Bladder Activity With RhPSMA 7.3: Comparison of 18F-RhPSMA 7.3 PET/CT With and Without Furosemide in Biochemical Recurrence of Prostate Cancer
Phase: PHASE2
Conditions: Prostate Adenocarcinoma, Recurrent Prostate Carcinoma
Sponsor: Emory University

Protocol Title:   Strategy to Reduce Bladder Activity with rhPSMA 7.3: Comparison of 18F-rhPSMA 
7.3 PET/CT with and without Furosemide in Biochemical Recurrence of Prostate Cancer
Page 1 of 38
Protocol Version: Version 6: JUN/6/2024
PROTOCOL TITLE: Strategy to Reduce Bladder Activity with rhPSMA 7.3: Comparison of 18F-
rhPSMA 7.3 PET/CT with and without Furosemide in Biochemical Recurrence of Prostate Cancer
WINSHIP PROTOCOL #:
COORDINATING CENTER: Emory University Healthcare, Atlanta, GA
PRINCIPAL INVESTIGATOR:
Name: David M. Schuster, MD, FACR 
Address: Division of Nuclear Medicine and Molecular Imaging, Department of Radiology and 
Radiological Sciences, 1364 Clifton Road, NE; Suite E163, Atlanta, GA 30322
Telephone: 404-712-4843; Fax: 404-712-7435
e-mail address: dschust@emory.edu
CO-INVESTIGATORS:
Name: Charles Marcus, MD
Department: Division of Nuclear Medicine and Molecular Imaging, Department of Radiology and 
Radiological Sciences, 1364 Clifton Road, NE; Suite E163, Atlanta, GA 30322
Telephone Number: 404-712-4843; Fax: 404-712-7435
Email Address: cvmarcu@emory.edu
Name: Ashesh B. Jani, MD, MSEE
Address: Department of Radiation Oncology, 1365 Clifton Road NE, Suite A1300, Atlanta, GA 30322
Telephone: 404-778-3827
e-mail address: abjani@emory.edu
STATISTICIAN:
Name: Jeffery M. Switchenko
Address: 718 Gatewood Road NE, Room 104, Atlanta, GA 30322 
Telephone: 404-778-4157 
e-mail address: jswitch@emory.edu
VERSION:  Version 6: JUN/6/2024

Protocol Title:   Strategy to Reduce Bladder Activity with rhPSMA 7.3: Comparison of 18F-rhPSMA 
7.3 PET/CT with and without Furosemide in Biochemical Recurrence of Prostate Cancer
Page 2 of 38
Protocol Version: Version 6: JUN/6/2024
FUNDING SOURCE: Blue Earth Diagnostics (BED IIT-439)
INVESTIGATIONAL PRODUCT (IP): 18F-rhPSMA 7.3 PET/CT, Blue Earth Diagnostics.
OTHER AGENT(S):  N/A
IND #: 162587; Sponsor-Investigator: David Schuster, MD
☐  Study Exempt from IND Requirements per 21 CFR 312.2(b).  
REVISION HISTORY
Revision #
Version Date
Summary of Changes
1
JUN/06/2023
e-Consent process option has been added to Section 15. 
Consent Process on page 33.
2
JUN/13/2023
Change inclusion criteria to patients with detectable serum 
PSA >0.1ng/mL following prostatectomy for prostate 
cancer.
3
JUL/10/2023
The PI made the edit to the protocol stating 2 weeks after 
the second PET/CT.
4
DEC/13/2023
Edits clarifying follow-up after each PET/CT for 
consistency with the study schema, pertinent medical 
history, urinary incontinence, removal of SOC saline 
flushes in the procedures
5
JUN/6/2024
The PI is switched to David Schuster.
The Sponsor-Investigator is switched to David Schuster as 
he is the new IND162587 Holder.

Protocol Title:   Strategy to Reduce Bladder Activity with rhPSMA 7.3: Comparison of 18F-rhPSMA 
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Protocol Version: Version 6: JUN/6/2024
Table of Contents
1.
Study Summary................................................................................................................................4
1.1  Synopsys ........................................................................................................................................4
1.2  Schema...........................................................................................................................................5
1.3  Schedule of Assessments ...............................................................................................................6
2.
Objectives (and Endpoints) .............................................................................................................7
3.
Background.......................................................................................................................................8
3.1 Study Rationale...............................................................................................................................8
3.2 Clinical Experience.........................................................................................................................8
4.
Study Intervention/Investigational Agent......................................................................................9
4.1 Description......................................................................................................................................9
4.2 Drug/Device Handling ....................................................................................................................9
4.3 Accountability.................................................................................................................................9
5.
Procedures Involved.......................................................................................................................10
5.1 Study Design.................................................................................................................................11
5.2 Dosing and Administration ...........................................................................................................11
5.3 Risks and/or Adverse events .........................................................................................................13
5.4 Dose Modification.........................................................................................................................14
5.5 Concomitant medication ...............................................................................................................15
5.6 Study Procedures ..........................................................................................................................15
5.7 Description of Study Procedures...................................................................................................17
6.
Data and Specimen Banking .........................................................................................................18
7.
Sharing of Results with Participants............................................................................................19
8.
Study Timelines ..............................................................................................................................19
8.1 Duration of therapy.......................................................................................................................20
8.2 Duration of follow-up ...................................................................................................................20
9.
Inclusion and Exclusion Criteria ..................................................................................................21
10. Vulnerable Populations .................................................................................................................22
11. Local Number of Participants.......................................................................................................23
12. Recruitment Methods ....................................................................................................................23
13. Withdrawal of Participants...........................................................................................................25
14. Risks to Participants ......................................................................................................................25
15. Potential Benefits to Participants..................................................................................................26
16. Data Management and Confidentiality........................................................................................26
16.1 Statistical consideration section: Biostatistician .........................................................................26
16.2 Data/specimens: ..........................................................................................................................26
17. Provisions to Monitor the Data to Ensure the Safety of Participants .......................................27
18. Provisions to Protect the Privacy Interests of Participants........................................................36
19. Economic Burden to Participants.................................................................................................37
20. Consent Process..............................................................................................................................37
21. Setting..............................................................................................................................................40
22. Resources Available .......................................................................................................................41
23. Multi-Site Research when Emory is the Lead Site......................................................................42
24. References .......................................................................................................................................44
APPENDIX A PERFORMANCE STATUS CRITERIA...................................................................44
APPENDIX B Drug Diary.....................................................................................................................46

Protocol Title:   Strategy to Reduce Bladder Activity with rhPSMA 7.3: Comparison of 18F-rhPSMA 
7.3 PET/CT with and without Furosemide in Biochemical Recurrence of Prostate Cancer
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APPENDIX C         Abbreviations and definition of terms................................................................47
1. Study Summary
1.3 1.1 Synopsys
Title:
Strategy to Reduce Bladder Activity with rhPSMA 7.3: Comparison of 18F-
rhPSMA 7.3 PET/CT with and without Furosemide in Biochemical Recurrence of 
Prostate Cancer
Study 
Description:
This research study is a single arm, Phase II study, designed to evaluate if 
administering furosemide at the time of 18F-rhPSMA 7.3 administration for 
PET/CT evaluation of prostate cancer patients with biochemical recurrence, 
significantly reduces bladder activity compared with the same patient scanned 
without furosemide as internal control
Objectives:
Primary Objective:   
To determine if administering 20 mg furosemide IV at the time of radiotracer 
injection significantly reduces bladder activity compared with the same patient 
scanned without furosemide as internal control
Secondary Objectives:

To compare detection rates of recurrent disease in blinded interpretations 
between the furosemide and non-furosemide 18F-rhPSMA-7.3 PET/CT 
scans, with patients serving as their own internal controls

To compare reader confidence in identifying prostate bed and other recurrent 
lesions on a 18F-rhPSMA-7.3 PET/CT with furosemide compared with 18F-
rhPSMA-7.3 PET/CT without furosemide
Endpoints:
Primary Endpoint:  
Determine the difference in the urinary bladder activity on 18F-rhPSMA-7.3 
PET/CT with furosemide compared with 18F-rhPSMA-7.3 PET/CT without 
furosemide in biochemical recurrence of prostate cancer post radical prostatectomy 
(Specific Aim 1).
Secondary Endpoints: 
Compare lesion detection and confidence between rhPSMA7.3 PET without and 
with furosemide. 
Study 
Population:
The patient population consists of 20 subjects ≥18 years of age with biochemical 
recurrence of prostate cancer after radical prostatectomy. 
Phase:
Phase II
Description of 
Sites/Facilities 
Enrolling 
Participants:

Emory University Hospital, Clifton Campus

Emory University Hospital Midtown

Emory University Hospital Johns Creek

Emory University Hospital St. Joseph’s

Protocol Title:   Strategy to Reduce Bladder Activity with rhPSMA 7.3: Comparison of 18F-rhPSMA 
7.3 PET/CT with and without Furosemide in Biochemical Recurrence of Prostate Cancer
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Description of 
Study 
Intervention:
Radiotracer production: Blue Earth Diagnostics Ltd, manufacturers of 18F-rhPSMA-
7.3, has pledged support with gratis radiotracer unit doses supplied from PET-NET 
Solutions, a commercial radiopharmacy who made similar unit doses under IND 
#141561 for the Phase 3 trial also completed at our center. This study IND #162587 
is held by Dr. David Schuster.
Study 
Duration:
5 years

Protocol Title:   Strategy to Reduce Bladder Activity with rhPSMA 7.3: Comparison of 18F-rhPSMA 
7.3 PET/CT with and without Furosemide in Biochemical Recurrence of Prostate Cancer
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1.4 1.2  Schema
Patient 
consent/eligibility/enrollment:
Adenocarcinoma of prostate, post RP
Detectable PSA
Group A 
(n=10)
Group B 
(n=10)
Study Visit 1 (1-30 days after 
consent/screening)
Complete 18F-rhPSMA-7.3 PET/CT 
#1 with furosemide
Study Visit 1 (1-30 days after 
consent/screening)
Complete 18F-rhPSMA-7.3 PET/CT 
#1 without furosemide
Study Visit 2 (2-7days after 
PET/CT #1)
Complete 18F-rhPSMA-7.3 PET/CT 
#2 without furosemide
Study Visit 2 (2-7days after 
PET/CT #1)
Complete 18F-rhPSMA-7.3 PET/CT 
#2 with furosemide.
Follow-up
Phone call from study nurse (1-3 
business days) after each PET/CT
Image and Data Analysis
Image Analysis: 2 nuclear medicine 
physicians will perform independent 
blinded interpretations of all PET/CT 
studies. Then consensus interpretation of 
both studies. 

Protocol Title:   Strategy to Reduce Bladder Activity with rhPSMA 7.3: Comparison of 18F-rhPSMA 
7.3 PET/CT with and without Furosemide in Biochemical Recurrence of Prostate Cancer
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1.5 1.3 Schedule of Assessments
Procedures
Enrollment/Screening (-30 
days)
Study Visit 1 
       PET/CT 1 
(Within 30 days of 
enrollment)
(Study Visit 2  
      PET/CT 2
(Within 2-7 days of Visit 1)
Follow up
(1-3 business days after 
each PET/CT)
Informed consent
X
Demographics
X
Pertinent Medical 
history
X
Administer study 
intervention
X
X
AE assessment
X
X
X
Complete Case Report 
Forms (CRFs)
X
X
X
X

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2. Objectives (and Endpoints)
OBJECTIVES
ENDPOINTS
Primary
1. To determine if administering 20 mg 
furosemide IV at the time of radiotracer 
injection significantly reduces bladder 
activity compared with the same patient 
scanned without furosemide as internal 
control
20 patients with biochemical recurrence of 
prostate cancer following radical prostatectomy 
will be sequentially assigned to either undergo 
18F-rhPSMA-7.3 PET/CT without furosemide 
first followed by a second PET/CT with 
furosemide at 2-7 days afterward, or vis-versa 
(10 in each group). Patients will be encouraged 
to void during the uptake phase up to 15 
minutes before being placed on the scanner for 
imaging. Bladder activity (SUVmax, SUVmean, 
and bladder volume), ureteral activity 
(SUVmax, SUVmean), as well as renal activity 
(SUVmax, SUVmean), will be recorded. The 
presence and degree of halo artifacts around the 
bladder and kidney will also be recorded. 
Exclusion criteria for this trial will include 
urinary incontinence that may interfere with 
performing the study and contraindications to 
furosemide. As always, patients will be 
encouraged to arrive well hydrated and to drink 
an additional 500-1000 ml of water during the 
uptake phase. 
Determine the difference in the urinary 
bladder activity on 18F-rhPSMA-7.3 
PET/CT with furosemide compared with 
18F-rhPSMA-7.3 PET/CT without 
furosemide in biochemical recurrence of 
prostate cancer post radical prostatectomy 
(Specific Aim 1).
Secondary
1. To compare detection rates of 
recurrent disease in blinded 
interpretations between the 
furosemide and non-furosemide 18F-
rhPSMA-7.3 PET/CT scans, with 
patients serving as their own internal 
controls
Lesion detection rates on a patient and region 
basis will be recorded in addition to the ratio of 
Compare lesion detection and confidence 
between rhPSMA7.3 PET without and with 
furosemide

Protocol Title:   Strategy to Reduce Bladder Activity with rhPSMA 7.3: Comparison of 18F-rhPSMA 
7.3 PET/CT with and without Furosemide in Biochemical Recurrence of Prostate Cancer
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OBJECTIVES
ENDPOINTS
the lesion to background activity including 
blood pool, liver, spleen and parotid. Test retest 
of lesions and background measurements 
between the studies with furosemide and 
without furosemide will be performed.
2. To compare reader confidence in 
identifying prostate bed and other 
recurrent lesions on a 18F-rhPSMA-
7.3 PET/CT with furosemide 
compared with 18F-rhPSMA-7.3 
PET/CT without furosemide
The readers’(total two readers) confidence in 
the assessment of findings in the prostate bed 
and other locoregional and distant lesions will 
be rated using a five-point Likert scale with 1 
being definitely benign and 5 being definitely 
malignant. The readers’ confidence scores for 
both the PET/CT scans (with and without 
furosemide) will be compared. The readers will 
be blinded to the furosemide injection.
Tertiary/Exploratory 
2. Background
Prostate cancer is the most common cancer diagnosed in men in 2021 and accounted for 11% of all 
cancer-related deaths in men in the United States. Early diagnosis is desirable so that definite treatment 
with curative intent can be offered. RP is a suitable definitive therapy offered to patients with early-
stage disease. Complete tumor resection during RP with or without pelvic lymph node dissection 
results in serum PSA level decline below detectable limits. PSA can then subsequently be used as a 
sensitive and specific tumor marker in the early detection of disease recurrence. The American 
Urological Association and European Association of Urology guidelines define biochemical recurrence 
after RP as an initial PSA value of 0.2 ng/mL or greater, measured 6 weeks after surgery to allow 
appropriate washout of any residual PSA. This result is confirmed by a subsequent PSA value of 
0.2ng/mL or greater to rule out a laboratory error[1, 2]. The risk of biochemical recurrence is associated 
with the baseline risk categorization of the disease, with patients in higher-risk groupings having 

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7.3 PET/CT with and without Furosemide in Biochemical Recurrence of Prostate Cancer
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shorter biochemical failure-free survival. Following confirmation of biochemical failure with a rising 
serum PSA level, imaging is used to localize the recurrent lesion and for the planning of salvage 
therapy. Early detection of recurrent disease is vital as lesions at this stage of the disease tend to be 
localized to the pelvis (prostate bed and pelvic lymph nodes), making targeted salvage therapy with 
curative intent feasible. 
Recent advances in functional imaging of prostate cancer recurrence with PET/CT have identified 
two groups of radionuclides with superior performance for localizing the site of recurrence of prostate 
cancer. 18F-fluciclovine, a radiolabeled synthetic amino acid developed and validated at Emory 
University Hospital, targets amino acid uptake by prostate cancer cells [3]. 18F-fluciclovine PET/CT 
performs better than conventional imaging and, when used to guide salvage radiotherapy, leads to 
favorable treatment outcomes[4]. One of the strengths of 18F-fluciclovine PET/CT in prostate cancer 
imaging is its lack of significant early urinary excretion [5]. The second category of approved 
radionuclides for BCR of prostate cancer imaging targets PSMA, a transmembrane protein significantly 
overexpressed in prostate cancer cells. 68Ga-PSMA is one such agent in this group with a high lesion 
detection rate at low serum PSA levels[6]. 68Ga-PSMA and 18F-DCFPyL, the two FDA-approved 
PSMA-targeting radionuclides, have a high urinary excretion with a potential for limiting the accurate 
detection of prostate bed recurrence.
Efforts are ongoing towards improving the detection rates of PSMA targeted imaging of BCR of 
prostate cancer. The desirable radioligand should preferably be labeled to F-18 and have low renal 
excretion into the urinary bladder. 18F-PSMA-1007 is a PSMA ligand labeled with F-18 and is excreted 
mostly via the biliary route. While these kinetic characteristics make it suitable, especially in the 
assessment of prostate bed recurrence, a high incidence of non-specific 18F-PSMA-1007 uptake 
especially in bones leading to a high false positivity rate has been a significant drawback[7, 8]. 
Radiohybrid (rhPSMA) is a new class of PSMA-targeting radioligand. rhPSMA ligands are not only 
suitable for labeling with F-18, but the molecule can be labeled with diagnostic and therapeutic 
radiometals[9, 10]. Coming in the wake of the recent FDA approval of PSMA-targeted radionuclide 
therapy for metastatic castration-resistant prostate cancer (mCRPC), rhPSMA is a true theranostic agent 
where the same molecule labeled with a diagnostic radionuclide such as F-18 can be used for imaging 
and labeled to a therapeutic radionuclide such as Lutetium-177.  In a recent study of 261 patients with 
BCR of prostate cancer after RP and a median serum PSA level of 0.96 ng/mL, 18F-rhPSMA-7 PET/CT 
detected disease recurrence in 81% of patients. Stratified according to serum PSA levels, the detection 
rates were 71%, 86%, 86%, and 95% at PSA levels of 0.2 to <0.5 ng/mL, 0.5 to <1 ng/mL, 1 to <2 
ng/mL, and ≥2 ng/mL, respectively[11]. There are four stereoisomers of rhPSMA-7, of which 
rhPSMA-7.3 has shown to be the preferred molecule based on its higher uptake in tumor, lower uptake 
by the kidneys, and improved clearance from the background[12]. In a single-center retrospective 
review of 242 patients with a median PSA level of 0.6 ng/mL who were imaged with 18F-rhPSMA-7.3 
PET/CT for the localization of the site of recurrence of prostate cancer, Rauscher and colleagues 
reported an overall positivity rate of 72.7%. At serum PSA levels of 0.2 to <0.5, 0.5 to <1, 1 to <2, and 
≥2 ng/mL, lesion detection rates were 61.8%, 67.9%, 81.1%, and 95.7%, respectively[13]. 
Based on the encouraging diagnostic performance of 18F-rhPSMA-7.3 PET/CT for the localization of 
BCR of prostate cancer, prospective trials have been undertaken to confirm these earlier results. In a 
phase 1 trial evaluating the safety, biodistribution, and radiation dosimetry of 18F-rhPSMA-7.3 in 
healthy adult volunteers, Tolvanen and colleagues reported that 18F-rhPSMA-7.3 was well tolerated in 
all volunteers (a single case of mild headache not requiring medication for treatment was judged to be 
due to rhPSMA-7.3 injection while others were not) with a calculated effective dose of 0.0141 
mSv/MBq, which is lower compared to effective dose due of other PSMA ligands [10]. 18F-rhPSMA-
7.3 showed a urinary route of excretion with bladder activity seen from 7 minutes post tracer injection, 

Protocol Title:   Strategy to Reduce Bladder Activity with rhPSMA 7.3: Comparison of 18F-rhPSMA 
7.3 PET/CT with and without Furosemide in Biochemical Recurrence of Prostate Cancer
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which increased progressively thereafter. The renal urinary excretion of 18F-rhPSMA-7.3 was lower 
compared with excretion of other PSMA ligands such as 68Ga-PSMA-11 and 18F-DCFPyL, but higher 
than that of 18F-PSMA-1007[10]. Continued effort geared towards a further reduction in the urinary 
excretion of 18F-rhPSMA-7.3 is pertinent to improve detection rates. 
Forced diuresis with co-administration of furosemide and the radiotracer is a strategy that has been 
explored in decreasing the urinary activityof other PSMA radioligands with a urinary route of 
excretion. In a study comparing the local prostate bed recurrence detection between patients who 
received hydration and furosemide administration at the time of 68Ga-PSMA-11 injection versus 
patients who did not, Uprimmy et al. reported a higher local prostate bed recurrence detection in 
patients who received hydration with intravenous furosemide versus patients who did not (25.5% 
versus 17.3%, p=0.048)[14]. The frequency of equivocal findings for prostate bed recurrence was more 
prevalent among patients who did not receive furosemide injection compared with those who did 
(16.8% versus 12.3%). Lower urinary activity did not influence the intensity of tracer uptake in prostate 
cancer recurrent lesions between the two groups with comparable SUV max in recurrent lesions. 
Similar improved diagnostic confidence with the assessment of disease in the prostate bed has been 
reported in other studies[15]. In an analysis of data from Technical University of Munich, a cohort of 
17 patients imaged with 18F-rhPSMA-7 (White Paper Prepared for Syncona: Evaluation of 18F-
rhPSMA7, Unpublished) demonstrated bladder SUVmean mean (SD) (range): 4.57 (6.4) (1.4-28.8). 
Yet as shown in a subanalysis, this lower bladder activity is highly dependent on the use of furosemide. 
Mean bladder SUV mean (n=5) without furosemide is 9.24, while with furosemide (n=12), bladder 
SUVmean is 2.63. In the joint guidelines of the European Association of Nuclear Medicine (EANM) 
and the Society of Nuclear Medicine and Molecular Imaging (SNMMI), the use of furosemide was 
recommended for 68Ga-PSMA-11 PET/CT imaging of prostate cancer[16].
2.3 3.1 Study Rationale
We hypothesize that the administration of intravenous furosemide at the time of radiotracer injection will 
reduce the activity of 18F-rhPSMA-7.3 in the urinary bladder and facilitates the identification of prostate 
bed recurrence in men with rising serum PSA post-prostatectomy. We also hypothesize that reduced 
urinary activity of 18F-rhPSMA-7.3 will improve readers’ confidence in assessing prostate bed 
recurrence of prostate cancer. An improved lesion detection will influence management decisions.
To test these hypotheses with the highest scientific rigor, we propose a study including men with BCR 
post-prostatectomy. Each patient will undergo two sets of 18F-rhPSMA-7.3 PET/CT scans, one with and 
the other without furosemide, and the level of urinary bladder activity, the detection rate of prostate bed 
recurrence and other lesions, will be compared between the two scans. In this manner, each patient will 
serve as their own control. We expect that the results from this study may generate sufficient evidence 
that may affect the workflow of 18F-rhPSMA-7.3 PET/CT imaging of BCR of prostate cancer, especially 
after FDA approval for use in routine clinical care.
2.4 3.2 Clinical Experience
Our preliminary data support a key scientific premise that the intravenous administration of 
furosemide at the time of radiotracer injection leads to lower radiotracer concentration in the urinary 
bladder. This finding is supported by published studies in the literature showing that intravenous 
administration of furosemide at the time of 68Ga-PSMA-11 administration causes a reduction in 

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bladder activity, improves detection of local prostate bed recurrence, and improves reader confidence. 
Study Intervention/Investigational Agent
2.5 4.1 Description
IV injection of 8 mCi (296 MBq) ± 20% of rhPSMA-7.3 (18F) diluted up to 10 mL will be used 
for each of the two PET scans. This dose is based on dosimetry data obtained from published 
phase I study data [21], and the dose utilized in the approval phase III trial that was recently 
concluded [NCT04186845]. The study will be performed under IND #162587 held by Dr. 
David Schuster.
2.6 4.2 Drug/Device Handling

Radiotracer handling and administration: Each individual dose of radiotracer will 
be specifically ordered and delivered on the day of the study for the research 
subject and administered by authorized personnel per standard radiotracer 
administration protocol of the institution and division.

The IND for the study is held by Dr. David Schuster (IND #162587)
2.7 4.3 Accountability
The study drug provided for this study will be supplied by a 3rd party radiopharmacy. The pharmacy will 
utilize a single-use cassette-based proprietary automated synthesis platform for radiolabeling, 
purification, and formulation (Scintomics GRP; Scintomics GmbH) and using an in-house remotely 
operated sterile filtration device for aseptic filling, in accordance with good manufacturing practices and 
according to the facility’s standard operating procedures. The study drug is single-use, and any remaining 
drug will be destroyed as directed in the IB. The PI is responsible for maintaining strict control over the 
investigational drug to ensure that it is used only for subjects enrolled in the study. The principal 
investigator or health care providers on the research team will administer study drug by injection.  Study 
site personnel will account for all study drugs received at the site.
Study drug will be kept in an appropriate, secure locked area and stored in accordance with the conditions 
specified on the labels. The PI or designated study personnel will maintain an accurate record of 
dispensing the study drug/s in a Drug Accountability Log.
The Drug Accountability Log will capture the following: 
• Records of product delivery, inventory, temperature monitoring, destruction, and return.
• Dosages prepared, time prepared, doses dispensed. 
• Doses and/or vials destroyed. 
• The Drug Accountability Log may be reviewed by the monitor during site visits and at the completion 
of the study.
Drug dispensing will also be captured in the source document at each patient visit. Drug accountability 
may be noted by the internal monitor during site visits and at the completion of the study. 

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3. Procedures Involved
Overall Design
We will undertake a study with 20 patients with biochemical recurrence of prostate cancer status post 
radical prostatectomy. Consideration for inclusion in this study will be based on detectable PSA after 
radical prostatectomy (PSA ≥ 0.1 ng/ml). Histology proof of recurrence will not be required. All 
patients will be recruited from the radiation oncology unit and other oncology units under Emory 
Healthcare. All 20 patients will undergo two sets of 18F-rhPSMA-7.3 PET/CT scans, one with and the 
other without intravenous administration of 20 mg of furosemide at the time of radiotracer injection. 
All patients will have oral hydration with 500 to 1000 ml of water during the uptake phase. The first set 
of 10 patients will have a 18F-rhPSMA-7.3 PET/CT without-furosemide followed by a 18F-rhPSMA-7.3 
PET/CT with-furosemide 2-7 days afterward. The second set of 10 patients will have their two 18F-
rhPSMA-7.3 PET scans in the reverse order, with-furosemide first followed by without-furosemide 2-7 
days afterward. Vital signs will be measured before and after each radiotracer administration. Each 
patient will undergo both imaging techniques, and the results will be interpreted blindly. A minimum of 
2 days is required between the two 18F-rhPSMA-7.3 to allow for the complete decay of the radiotracer 
from the first scan before the second scan (physical half-life of 18F is 110 minutes). Patients will be 
allowed to void during the 60-70 minutes uptake period between 18F-rhPSMA-7.3 radiotracer 
administration and the commencement of PET/CT imaging. Patients will be encouraged to void at 
approximately 50 minutes post injection and encouraged to refrain from voiding 15 minutes before the 
commencement of the PET/CT (60-70 min post injection), if possible, to facilitate bladder distension.
Two nuclear medicine physicians, Drs. Marcus and Schuster, who are coinvestigators in this work, will 
independently interpret the two scans of the entire 20 patients within 2 weeks of completion of the 2nd 
PET/CT for each patient.  The readers will be blinded to all imaging and furosemide administration, 
including the other PET/CT done as part of the study. All suspicious lesions with non-physiologic 
activity above background for loco-regional spread and distant disease will be identified and rated for 
suspicion of malignancy on a 5-point Likert scale (where 1 = definitely benign and 5 = definitely 
malignant). Image interpretation will be done on an advanced workstation (MIM Software). Metabolic 
parameters (SUV max, SUV mean, SUVpeak of all identified lesions with be determined and recorded. 
The bladder volume on each scan will be determined and recorded. SUV max and SUV mean of 
background organs, including the parotid, aortic arch, liver, spleen, kidney, ureters and the urinary 
bladder, will be determined and recorded. The presence and degree of dropout or halo artifacts around 
the bladder and kidney will also be recorded. After the individual blind reads, the two readers will 
perform an unblinded consensus read for the reconciliation interpretation of the two scans for each 
patient. Concordant and discordant lesions between each PET/CT study and conventional imaging will 
be reported.
Scientific Rationale for Study Design
Our preliminary data support a key scientific premise that the intravenous administration of furosemide 
at the time of radiotracer injection leads to lower radiotracer concentration in the urinary bladder. This 
finding is supported by published studies in the literature showing that intravenous administration of 
furosemide at the time of 68Ga-PSMA-11 administration causes a reduction in bladder activity, 

Protocol Title:   Strategy to Reduce Bladder Activity with rhPSMA 7.3: Comparison of 18F-rhPSMA 
7.3 PET/CT with and without Furosemide in Biochemical Recurrence of Prostate Cancer
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Protocol Version: Version 6: JUN/6/2024
improves detection of local prostate bed recurrence, and improves reader confidence. We hypothesize 
that the administration of intravenous furosemide at the time of radiotracer injection will reduce the 
activity of 18F-rhPSMA-7.3 in the urinary bladder and facilitates the identification of prostate bed 
recurrence in men with rising serum PSA post-prostatectomy. We also hypothesize that reduced urinary 
activity of 18F-rhPSMA-7.3 will improve readers’ confidence in assessing prostate bed recurrence of 
prostate cancer. An improved lesion detection will influence management decisions.
To test these hypotheses with the highest scientific rigor, we propose a study including men with BCR 
post-prostatectomy. Each patient will undergo two sets of 18F-rhPSMA-7.3 PET/CT scans, one with 
and the other without furosemide, and the level of urinary bladder activity, the detection rate of prostate 
bed recurrence and other lesions, will be compared between the two scans. In this manner, each patient 
will serve as their own control. We expect that the results from this study may generate sufficient 
evidence that may affect the workflow of 18F-rhPSMA-7.3 PET/CT imaging of BCR of prostate cancer, 
especially after FDA approval for use in routine clinical care. 
Justification for Dose
IV injection of 8 mCi (296 MBq) ± 20% of rhPSMA-7.3 (18F) diluted up to 10 mL will be used for each 
of the two PET scans. This dose is based on dosimetry data obtained from published phase I study data 
[21], and the dose utilized in the approval phase III trial that was recently concluded [NCT04186845]. 
The study will be performed under IND #162587 held by Dr. David Schuster. 
PET Acquisition
18F-rhPSMA-7.3 PET/CT Imaging: PET/CT will be acquired on a state-of-the-art GE Discovery 690 
TOF PET-CT scanner at Emory University Hospital or similar device. Patients do not need to fast prior 
to the scans. All patients will receive one PET/CT scan with 20mg furosemide administered 
intravenously at the time of radiotracer administration and will be encouraged to orally hydrate with 
500-1000mL of water during the uptake phase of 60-70 minutes. Patients will be encouraged to void 
during the uptake phase up to 15 minutes prior to the commencement of the scan, if possible. PET 
images will be acquired from proximal thigh to skull base, approximately 3 minutes per bed position. 
All PET scans will be acquired in a 3-dimensional mode and the emission data will be corrected for 
randoms, dead time, scatter and attenuation. The images will be reconstructed using an iterative 
algorithm. Vital signs will be measured before and after administration of the radiotracer.
End of Study Definition
The study will be closed to recruitment once all 20 patients have been recruited, scanned with the 2 
PET/CTs each and have completed follow-up (1-3 business days after each PET/CT). The study will be 
formally closed once all manuscripts have been published and all follow-up completed. There will be 
no other study-specific visits after the second PET/CT scan (visit 2), though the patient will be called 
by the study nurse within 1-3 business days after each study to ensure no delayed AEs occurred. The 
follow-up phone call for one study will be performed before the patient undergoes the subsequent scan.
3.3 5.2 Dosing and Administration
IV injection of 8 mCi (296 MBq) ± 20% of rhPSMA-7.3 (18F) diluted up to 10 mL will be used for 
each of the two PET scans. This dose is based on dosimetry data obtained from published phase I study 
data [21], and the dose utilized in the approval phase III trial that was recently concluded 
[NCT04186845]. The study will be performed under IND #162587 held by Dr. David Schuster.

Protocol Title:   Strategy to Reduce Bladder Activity with rhPSMA 7.3: Comparison of 18F-rhPSMA 
7.3 PET/CT with and without Furosemide in Biochemical Recurrence of Prostate Cancer
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Protocol Version: Version 6: JUN/6/2024
3.4 5.3 Risks and/or adverse events 

Radiation Risks: The principal risk associated with a radiation dose is the 
possibility of developing radiation-induced cancer later in life. However, the 
additional risk of radiation-induced cancer from these diagnostic procedures 
is low compared to the risks from the disease itself. Human dosimetry data 
for 18F-rhPSMA-7.3 from the phase I study of Tolvanen and co-
workers[18]: The (radiation absorbed) effective dose from the administration 
of 225 MBq of 18F-rhPSMA-7.3 is 0.0138 mSv/MBq at a 1-hour voiding 
interval. The organs with the highest absorbed radiation dose are the adrenals 
(0.184 mGy/MBq), the kidneys (0.172 mGy/MBq), and the submandibular 
glands (0.148 mGy/MBq).The effective dose from the CT component of the 
study is 15.7mSv.

Allergic or other reactions to radiotracer: The risk of AEs and SAEs from 
PET radiotracers is exceedingly low. A significant shift from baseline can be 
attributable to the radiotracer injection and not the patient’s medical 
condition will be considered an unexpected AE. An event greater than 24 hrs 
will not be considered related to study procedure AE since the radiotracer has 
effectively decayed by 20 hours. There have been no previous instances of 
allergic reactions. In prior studies where 18F-rhPSMA-7.3 was used in 
human subjects, the risk of adverse events which can be attributed to the 
radiotracer is extremely low, and of minimal medical impact such as burning 
at IV site or headache.

Risks related to IV for PET scan: A small amount of radioactive material will 
be injected by either a hand-held needle or a machine. Such injections are 
generally quite safe, but any injection involves some risks. The injection 
could harm a nerve, artery, or vein, or cause infection. The radioactive 
material could also leak from veins, causing swelling and discomfort.

False positive on PET: It is possible that a lesion identified on the 
experimental PET procedures may be false-positive, thus potentially leading 
to an inappropriate biopsy. While further evaluation of imaging finding to 
confirm true positivity may occur according to the standard of care practice, 
a biopsy of the imaging-identified lesion is not in the scope of this trial, nor is 
it a requirement.

Furosemide: The risk from the low dose (20mg) of furosemide is minimal. It 
will temporarily cause increased urination. Though unlikely, other side 
effects may include: nausea or vomiting, diarrhea, constipation, stomach 
cramping, vertigo, dizziness, headache, blurred vision, itching or rash. 
3.5 5.4 Dose Modification
Not applicable

Protocol Title:   Strategy to Reduce Bladder Activity with rhPSMA 7.3: Comparison of 18F-rhPSMA 
7.3 PET/CT with and without Furosemide in Biochemical Recurrence of Prostate Cancer
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Protocol Version: Version 6: JUN/6/2024
3.6 5.5 Concomitant medication
Not applicable
3.7 5.6 Study Procedures
Screening Phase
Adult patients with biochemical recurrence of prostate cancer, status post prostatectomy who meet the 
eligibility criteria will be enrolled in the study.
Inclusion Criteria
i.
Adenocarcinoma of the prostate, post-prostatectomy.
ii.
Biochemical recurrence of prostate cancer following RP with or without adjuvant or salvage 
therapy: PSA ≥0.1 ng/mL 
iii.
Age over 18.
iv.
Ability to provide written informed consent.
v.
Patients with standard of care creatinine ≤1.3mg/dL performed within 90 days prior to 
enrollment
Exclusion Criteria
i.
Inability to undergo 18F-rhPSMA PET-CT, contraindications to furosemide or urinary 
incontinence that may interfere with performing the study.
Study population:
_(Y) 1. Adult patients with a diagnosis of adenocarcinoma of the prostate, post radical prostatectomy
_(Y) 2. Biochemical recurrence as defined by PSA ≥ 0.1 
_(Y) 3. Age over 18 years and ability to give informed consent
_(N) 4. Inability to undergo 18F-rhPSMA-7.3 PET/CT
_(N) 5. Contraindications to furosemide such as true allergy or urinary incontinence that may interfere 
with performing the study
3.8 5.7 Description of Study Procedures
Overall Design
We will undertake a study with 20 patients with biochemical recurrence of prostate 
cancer status post radical prostatectomy. Consideration for inclusion in this study will be 
based on a detectable serum PSA after radical prostatectomy (PSA ≥ 0.1 ng/ml). 
Histology proof of recurrence will not be required. All patients will be recruited from 
the radiation oncology unit and other oncology units under Emory Healthcare. All 20 
patients will undergo two sets of 18F-rhPSMA-7.3 PET/CT scans, one with and the 
other without intravenous administration of 20 mg of furosemide at the time of 
radiotracer injection. All patients will have oral hydration with 500 to 1000 ml of water 
during the uptake phase. The first set of 10 patients will have a 18F-rhPSMA-7.3 
PET/CT without-furosemide followed by a 18F-rhPSMA-7.3 PET/CT with-furosemide 
2-7 days afterward. The second set of 10 patients will have their two 18F-rhPSMA-7.3 

Protocol Title:   Strategy to Reduce Bladder Activity with rhPSMA 7.3: Comparison of 18F-rhPSMA 
7.3 PET/CT with and without Furosemide in Biochemical Recurrence of Prostate Cancer
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Protocol Version: Version 6: JUN/6/2024
PET scans in the reverse order, with-furosemide first followed by without-furosemide 2-
7 days afterward. Vital signs will be measured before and after each radiotracer 
administration. Each patient will undergo both imaging techniques, and the results will 
be interpreted blindly. A minimum of 2 days is required between the two 18F-rhPSMA-
7.3 to allow for the complete decay of the radiotracer from the first scan before the 
second scan (physical half-life of 18F is 110 minutes). Patients will be allowed to void 
during the 60-70 minutes uptake period between 18F-rhPSMA-7.3 radiotracer 
administration and the commencement of PET/CT imaging. Patients will be encouraged 
to void at approximately 50 minutes post injection and encouraged to refrain from 
voiding 15 minutes before the commencement of the PET/CT (60-70 min post 
injection), if possible, to facilitate bladder distension.
Two nuclear medicine physicians, Drs. Marcus and Schuster, who are coinvestigators in 
this work, will independently interpret the two scans of the entire 20 patients.  The 
readers will be blinded to all imaging and furosemide administration, including the other 
PET/CT done as part of the study. All suspicious lesions with non-physiologic activity 
above background for loco-regional spread and distant disease will be identified and 
rated for suspicion of malignancy on a 5-point Likert scale (where 1 = definitely benign 
and 5 = definitely malignant). Image interpretation will be done on an advanced 
workstation (MIM Software). Metabolic parameters (SUV max, SUV mean, SUVpeak 
of all identified lesions with be determined and recorded. The bladder volume on each 
scan will be determined and recorded. SUV max and SUV mean of background organs, 
including the parotid, aortic arch, liver, spleen, kidney, ureters and the urinary bladder, 
will be determined and recorded. The presence and degree of dropout or halo artifacts 
around the bladder and kidney will also be recorded. After the individual blind reads, the 
two readers will perform an unblinded consensus read for the reconciliation 
interpretation of the two scans for each patient. Concordant and discordant lesions 
between each PET/CT study and conventional imaging will be reported.
Scientific Rationale for Study Design
Our preliminary data support a key scientific premise that the intravenous administration 
of furosemide at the time of radiotracer injection leads to lower radiotracer concentration 
in the urinary bladder. This finding is supported by published studies in the literature 
showing that intravenous administration of furosemide at the time of 68Ga-PSMA-11 
administration causes a reduction in bladder activity, improves detection of local 
prostate bed recurrence, and improves reader confidence. We hypothesize that the 
administration of intravenous furosemide at the time of radiotracer injection will reduce 
the activity of 18F-rhPSMA-7.3 in the urinary bladder and facilitates the identification 
of prostate bed recurrence in men with rising serum PSA post-prostatectomy. We also 
hypothesize that reduced urinary activity of 18F-rhPSMA-7.3 will improve readers’ 
confidence in assessing prostate bed recurrence of prostate cancer. An improved lesion 
detection will influence management decisions.
To test these hypotheses with the highest scientific rigor, we propose a study including 
men with BCR post-prostatectomy. Each patient will undergo two sets of 18F-rhPSMA-
7.3 PET/CT scans, one with and the other without furosemide, and the level of urinary 
bladder activity, the detection rate of prostate bed recurrence and other lesions, will be 
compared between the two scans. In this manner, each patient will serve as their own 

Protocol Title:   Strategy to Reduce Bladder Activity with rhPSMA 7.3: Comparison of 18F-rhPSMA 
7.3 PET/CT with and without Furosemide in Biochemical Recurrence of Prostate Cancer
Page 18 of 38
Protocol Version: Version 6: JUN/6/2024
control. We expect that the results from this study may generate sufficient evidence that 
may affect the workflow of 18F-rhPSMA-7.3 PET/CT imaging of BCR of prostate 
cancer, especially after FDA approval for use in routine clinical care. 
Justification for Dose
IV injection of 8 mCi (296 MBq) ± 20% of rhPSMA-7.3 (18F) diluted up to 10 mL will 
be used for each of the two PET scans. This dose is based on dosimetry data obtained 
from published phase I study data [21], and the dose utilized in the approval phase III 
trial that was recently concluded [NCT04186845]. The study will be performed under 
IND #162587 held by Dr. David Schuster. 
PET Acquisition
18F-rhPSMA-7.3 PET/CT Imaging: PET/CT will be acquired on a state-of-the-art GE 
Discovery 690 TOF PET-CT scanner at Emory University Hospital or similar device. 
Patients do not need to fast prior to the scans. All patients will receive one PET/CT scan 
with 20mg furosemide administered intravenously at the time of radiotracer 
administration and will be encouraged to orally hydrate with 500-1000mL of water 
during the uptake phase of 60-70 minutes. Patients will be encouraged to void during the 
uptake phase up to 15 minutes prior to the commencement of the scan, if possible. PET 
images will be acquired from proximal thigh to skull base, approximately 3 minutes per 
bed position. All PET scans will be acquired in a 3-dimensional mode and the emission 
data will be corrected for randoms, dead time, scatter and attenuation. The images will 
be reconstructed using an iterative algorithm. Vital signs will be measured before and 
after administration of the radiotracer.
End of Study Definition
The study will be closed to recruitment once all 20 patients have been recruited, scanned 
with the 2 PET/CTs each and have completed follow-up (1-3 business days after each 
PET/CT). The study will be formally closed once all manuscripts have been published 
and all follow-up completed. There will be no other study-specific visits after the second 
PET/CT scan (visit 2), though the patient will be called by the study nurse within 1-3 
business days after each study to ensure no delayed AEs occurred. The follow-up phone 
call for one study will be performed before the patient undergoes the subsequent scan.
3. Sharing of Results with Participants
PET findings will be used for research purposes within the context of the clinical trial as noted above. 
The key findings of the PET/CT and all incidental findings will be recorded in the clinical research form 
and emergent incidental findings will be communicated to the patient’s physician who is also an 
investigator in this study. The non-emergent findings will be conveyed to the patient at the discretion of 
the patient’s physician after a discussion of the risk versus benefit since this investigational radiotracer 
is not FDA approved for clinical use. 
Incidental Findings
a.   All incidental findings noted by the imager will be discussed with the attending physician who is 
a co-investigator and documented in the electronic medical record. 

Protocol Title:   Strategy to Reduce Bladder Activity with rhPSMA 7.3: Comparison of 18F-rhPSMA 
7.3 PET/CT with and without Furosemide in Biochemical Recurrence of Prostate Cancer
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Protocol Version: Version 6: JUN/6/2024
b.   The oncologist will educate the patient about the nature of the incidental finding, how to seek care 
from a clinician or specialist, obtaining health insurance to secure treatment, and/or referral to a 
clinical specialist, if one is required. 
c.   Language to this effect is present in the consent form.
4. Study Timelines
The total duration of the study is 5 years, with an accrual rate of approximately 4 patients per year. For 
the individual study participant, the patient participation is complete after the 2nd PET/CT study. 
However, the participating patients may be followed up for correlation for up to 5 years after the study. 
5. Inclusion and Exclusion Criteria
Adult patients with biochemical recurrence of prostate cancer, status post prostatectomy who meet the 
eligibility criteria will be enrolled in the study.
Inclusion Criteria
Adenocarcinoma of the prostate, post-prostatectomy.
Biochemical recurrence of prostate cancer following RP with or without adjuvant or salvage therapy: 
PSA ≥0.1 ng/mL 
Age over 18.
Ability to provide written informed consent.
Patients with standard of care creatinine ≤1.3mg/dL performed within 90 days prior to enrollment
Exclusion Criteria
Inability to undergo 18F-rhPSMA PET-CT, scontraindications to furosemide or urinary incontinence 
that may interfere with performing the study.
Population
_(Y) 1. Adult patients with a diagnosis of adenocarcinoma of the prostate, post radical prostatectomy
_(Y) 2. Biochemical recurrence as defined by PSA ≥ 0.1
_(Y) 3. Age over 18 years and ability to give informed consent
_(N) 4. Inability to undergo 18F-rhPSMA-7.3 PET/CT
_(N) 5. Contraindications to furosemide such as true allergy or urinary incontinence that may interfere 
with performing the study
6. Local Number of Participants
All 20 patients will be recruited from Emory Healthcare
7. Recruitment Methods
All patients will be recruited from the radiation oncology unit and other oncology units such as medical 
oncology and urology under Emory Healthcare
8. Withdrawal of Participants

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7.3 PET/CT with and without Furosemide in Biochemical Recurrence of Prostate Cancer
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Protocol Version: Version 6: JUN/6/2024
Anticipated withdrawal of patients is expected to be minimal in this small cohort of patients who will 
undergo a diagnostic PET/CT study. Anticipated causes include, unable to undergo PET/CT study due 
to issues with patient comfort such as severe claustrophobia. In case of early termination, the cause of 
the termination will be documented, and further imaging will not be performed.  If for some reason a 
patient is unable to complete the second study after the first, this will be considered a withdrawal and 
another patient will be recruited in their place.
9. Risks to Participants
1. Radiation Risks: The principal risk associated with a radiation dose is the possibility of 
developing radiation-induced cancer later in life. However, the additional risk of radiation-
induced cancer from these diagnostic procedures is low compared to the risks from the disease 
itself.
Human dosimetry data for 18F-rhPSMA-7.3 from the phase I study of Tolvanen and co-
workers[18]: The (radiation absorbed) effective dose from the administration of 225 MBq of 
18F-rhPSMA-7.3 is 0.0138 mSv/MBq at a 1-hour voiding interval. The organs with the highest 
absorbed radiation dose are the adrenals (0.184 mGy/MBq), the kidneys (0.172 mGy/MBq), and 
the submandibular glands (0.148 mGy/MBq).
The effective dose from the CT component of the study is 15.7mSv.
2. Allergic or other reactions to radiotracer: The risk of AEs and SAEs from PET radiotracers is 
exceedingly low. A significant shift from baseline can be attributable to the radiotracer injection 
and not the patient’s medical condition will be considered an unexpected AE. An event greater 
than 24 hrs will not be considered related to study procedure AE since the radiotracer has 
effectively decayed by 20 hours. There have been no previous instances of allergic reactions. In 
prior studies where 18F-rhPSMA-7.3 was used in human subjects, the risk of adverse events 
which can be attributed to the radiotracer is extremely low, and of minimal medical impact such 
as burning at IV site or headache.
3. Risks related to IV for PET scan: A small amount of radioactive material will be injected by 
either a hand-held needle or a machine. Such injections are generally quite safe, but any 
injection involves some risks. The injection could harm a nerve, artery, or vein, or cause 
infection. The radioactive material could also leak from veins, causing swelling and discomfort.
4. False positive on PET: It is possible that a lesion identified on the experimental PET procedures 
may be false-positive, thus potentially leading to an inappropriate biopsy. While further 
evaluation of imaging finding to confirm true positivity may occur according to the standard of 
care practice, a biopsy of the imaging-identified lesion is not in the scope of this trial, nor is 
it a requirement.
5. Furosemide: The risk from the low dose (20mg) of furosemide is minimal. It will temporarily 
cause increased urination. Though unlikely, other side effects may include: nausea or vomiting, 
diarrhea, constipation, stomach cramping, vertigo, dizziness, headache, blurred vision, itching 
or rash. 
10. Potential Benefits to Participants

Protocol Title:   Strategy to Reduce Bladder Activity with rhPSMA 7.3: Comparison of 18F-rhPSMA 
7.3 PET/CT with and without Furosemide in Biochemical Recurrence of Prostate Cancer
Page 21 of 38
Protocol Version: Version 6: JUN/6/2024
The primary benefit of participating in this study is more accurate localization of the site of 
BCR of prostate cancer which impacts the choice of patient management. Early BCR of prostate 
cancer occurs in the prostate bed, especially at the vesicourethral anastomosis. A full bladder 
with excreted radiotracer as is present with the commercially available PSMA radiotracers has 
the potential to obscure the visualization of this common site of recurrence. rhPSMA has been 
shown to have a high PPV for localization of prostate cancer lesions (ASCO-GU 2022)[17]. 
11. Data Management and Confidentiality
The study will be approved by the Emory IRB per standard institutional requirements and informed 
written consent obtained. 
To maintain patient confidentiality, medical records will be accessed only by IRB-approved study 
personnel (e.g. CRC). A partial HIPAA waiver will be obtained to allow screening of provider schedules 
for the identification of potentially eligible research subjects. Upon medical record review and 
identification of a potentially eligible research subject, the patient's full name, MRN, EMPI, and full dates 
(e.g., DOB, procedure dates, admission dates, etc.) will be stored on a screening log and used by study 
coordinators for the subsequent study activities. The screening log will be kept on the HIPAA compliant 
shared folder and will be accessible only to limited IRB-approved study personnel (e.g., CRC). Sensitive 
data will always be stored on the HIPAA compliant shared folder and will never be stored on local or 
portable drives that are not encrypted per Emory IS standards.
Each study participant will be assigned a unique study identification (ID) number at the time that 
informed consent is given. Personal identifying information and study data, including the unique study 
ID, will be entered in the Microsoft Database that will be kept on the HIPAA compliant shared folder 
accessible to approved study personnel only. Only de-identified data will be shared with those outside 
the study team to ensure adequate protection of sensitive data.
Study identifiers will be kept indefinitely. 
To maintain participant confidentiality, no identifying information about any of the study participants 
will be published. Any data published (including demographic information about the study sample as a 
whole) will be in aggregate/summary form only.
Plans to monitor the data to ensure safety of participants and data integrity
☐ No more than minimal risk - Study not required to follow DSMP guidance 
☒ More than minimal risk – Continue below.
Study Complexity 
☐ Medium Complexity
☒ High Complexity Category A
☐ High Complexity Category B

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Protocol Version: Version 6: JUN/6/2024
If choosing this category for a study under an IND or IDE because you believe the 
study intervention does not significantly impact morbidity or mortality, please 
provide your rationale:
Monitoring Table 2
DSMP Requirement
How this Requirement is Met 
Frequency
Responsible Party(ies)
Real-time review of 
participant data during 
initial data collection.
This requirement will be met 
per Winship’s NCI approved 
DSMP
This will occur 
every time new 
information is 
obtained.
DSMC
Site Monitoring at pre-
determined intervals: 
The Principal Investigator 
has a responsibility to 
ensure that the study is 
following all aspects of 
the protocol. 
This requirement will be met 
per Winship’s NCI approved 
DSMP
Biannually
DSMC
100% review of 
regulatory files
DSMC monitors will review the 
protocol, amendments, 
informed consent documents, 
IRB submissions and meet with 
the principal investigator for 
clarification of study objectives
Reviewed at first 
and close-out visits
DSMC
100% review of consent 
forms
Monthly QA check of 5-10 
randomly selected consents to 
validate Central Subject 
Registration (CSR) and PRMS to 
conduct QA consent checks in 
real time as subjects are 
registered in OnCore vis CSR 
process
Biannually
PRMS, QM
Review of credentials, 
training records, the 
delegation of 
responsibility logs (if 
applicable)
Clinical trials monitor will review 
the electronic regulatory binder 
and compare them against the 
staff listed on the DOA log. The 
monitor also reviews the site’s 
source documents to ensure 
that all study staff have been 
properly listed on the DOA and 
have corresponding 
documentation (CV, ML, GCP 
certs, training log) filed in the 
Biannually
DSMC

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7.3 PET/CT with and without Furosemide in Biochemical Recurrence of Prostate Cancer
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Protocol Version: Version 6: JUN/6/2024
electronic regulatory study 
binder
Comparison of case 
report forms (CRF) to 
source documentation 
for accuracy and 
completion
The PI is responsible for 
ensuring that instances of 
egregious data insufficiencies 
that may impact the scientific 
integrity of the trial
Biannually
DSMC
Review of 
documentation of all 
adverse events
During the monitoring process, 
the DSMB reviews trial safety 
data for stopping rules, 
deviations, study amendments, 
accrual rates and monitoring 
reports for therapeutic 
investigator-initiated clinical 
trials and any other trial as 
deemed necessary
Biannually
DSMC
Monitoring of critical 
data points (eligibility, 
study endpoints, etc.)
The assigned monitor will 
randomly select subject(s) for 
review based on parameters in 
Table 1 or 2 as noted above. 
Although the principal 
investigator and applicable 
study team members will 
receive notification of trial 
monitoring in advance, the 
subject selection will not be 
revealed in advance of the 
monitoring visit.
Biannually
DSMC
Laboratory review of 
processing and storage 
of specimens
The assigned monitor will 
randomly select subject(s) for 
review based on parameters in 
Table 1 or 2 as noted above
Reviewed at first 
and close-out visits 
and at least 
biannually
DSMC
Assessment of laboratory 
specimens stored locally
QM will monitor data entered 
into the study database against 
the site source documents, 
including laboratory reports. 
During visits to the laboratory, 
QM will ensure study specimens 
are being properly stored, 
handled and shipped according 
to the protocol and lab manual.
Reviewed at first 
and close-out visits 
and at least 
annually
Winship Quality 
Management 
Department
Test article 
accountability review
Clinical research pharmacy at 
Grady Memorial Hospital
Reviewed at first 
and close-out visits 
Research Pharmacist

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7.3 PET/CT with and without Furosemide in Biochemical Recurrence of Prostate Cancer
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Protocol Version: Version 6: JUN/6/2024
and at least 
biannually
Accountability logs, 
dispensing records, and 
other participant records 
QM will review accountability 
and dispensing log, including IP 
administration forms.
Annually
Winship Quality 
Management 
Department
For FDA regulated 
studies, the following 
requirements apply:
Monitoring activities meet the 
FDA's requirements as 
delineated in 21 CFR 50, 21 CFR 
56, 21 CFR 812 for studies 
conducted under an IDE and 21 
CFR 312 for studies conducted 
under an IND.
Biannually
DSMC
Monitoring methods 
(may include centralized, 
on-site, and self-
monitoring)
The internal monitoring team is 
independent from any study 
protocol and does not perform 
any trial-related specific duties 
in order to uphold an unbiased 
approach to study monitoring. 
Oversight of the monitoring 
process and 
identification/assignment of 
studies for monitoring is 
provided by the Manager of the 
Internal Monitors.
Biannually                   DSMC
*For international studies, you are required to engage a CRO that is working in the site country and/or to 
consult with Emory’s legal counsel regarding compliance with the country’s clinical research regulations.
                                                                                                                       

Protocol Title:   Strategy to Reduce Bladder Activity with rhPSMA 7.3: Comparison of 18F-rhPSMA 
7.3 PET/CT with and without Furosemide in Biochemical Recurrence of Prostate Cancer
Page 25 of 38
Protocol Version: Version 6: JUN/6/2024
Patients will be monitored by the technologists and/or study nurse before and after the studies for any 
adverse events/reactions. They will be given contact phone numbers to call if they experience any 
problems (i.e., problems with the IV site, any allergic reaction symptoms). Basic monitoring of adverse 
events during the 18F-rhPSMA-7.3 PET visit will be performed. This will consist of direct observation 
by our study staff during the visit with documentation of any adverse events or lack thereof in the 
electronic medical record. The physical half-life of the radiotracer is 110 minutes. Hence, adverse events 
are not expected to occur past 24 hrs after radiotracer administration.
Written IND safety reports will be submitted to the FDA by the IND sponsor, for serious, unexpected 
suspected adverse reactions within 15 calendar days of learning of its occurrence. If the event is fatal or 
is deemed to be life threatening, the report will be made within 7 calendar days.  The IND sponsor will 
also make an assessment of whether the event constitutes an unanticipated problem posing risks to 
subjects or others (UP). This assessment will be provided to the Emory University IRB, which, in turn 
will make a final determination.  If the Emory IRB determines an event is a UP it will notify the 
appropriate regulatory agencies and institutional officials.
In addition to reporting of Serious Adverse Events (SAEs) to the responsible IRB/IEC and Health 
Authority, Principal Investigator or designee will inform Blue Earth Diagnostics (BED) of all SAEs in 
connection with the Study that occur following receipt of rhPSMA-7.3, whether or not related to Product. 
PI or designee shall notify BED within twenty-four (24) hours of knowledge of any SAEs.  SAE reports 
to BED must be recorded and faxed or scanned and emailed to: 
Bracco Diagnostics Inc. Drug Safety Unit 
E mail:  Drugsafetyus@BlueEarthDx.com  
Fax:   +1-609-514-2522
To the extent permitted by federal law, additional and further requested information (follow-up or 
corrections to the original case) will be detailed and faxed/emailed to the same address and will include 
the following minimum information: The name and contact information of the reporter, the name of the 
study drug(s), a description of the reported SAE, with the patient identified by one or more of the 
following (patient initials/code, patient number  age, sex), an investigator assessment of study drug 
causality, and any additional data customarily accompanying such reports which would aid the review 
and causality assessment of the case including but not limited to the date of onset, severity, the time from 
administration of study drug(s) to start of the event, the duration and outcome of the event, any possible 
etiology for the event, and the final diagnosis or syndrome, if known.
Definition of unanticipated problems (UP) and reporting requirements
The Office for Human Research Protections (OHRP) considers unanticipated problems involving risks 
to participants or others to include, in general, any incident, experience, or an outcome that meets all the 
following criteria:  Unexpected in terms of nature, severity, or frequency given (a) the research 
procedures that are described in the protocol-related documents, such as the IRB-approved research 
protocol and informed consent document; and (b) the characteristics of the participant population being 
studied; Related or possibly related to participation in the research (“possibly related” means there is a 
reasonable possibility that the incident, experience, or outcome may have been caused by the procedures 
involved in the research); and suggests that the research places participants or others at a greater risk of 
harm (including physical, psychological, economic, or social harm) than was previously known or 
recognized.  This study will use the OHRP definition of unanticipated problems. Incidents or events that 
meet the OHRP criteria for UPs require the creation and completion of a UP report form. It is the site 

Protocol Title:   Strategy to Reduce Bladder Activity with rhPSMA 7.3: Comparison of 18F-rhPSMA 
7.3 PET/CT with and without Furosemide in Biochemical Recurrence of Prostate Cancer
Page 26 of 38
Protocol Version: Version 6: JUN/6/2024
investigator’s responsibility to report UPs to their IRB and to the DCC/study sponsor. The UP report will 
include the following information:  Protocol identifying information: protocol title and number, PI’s 
name, and the IRB project number; A detailed description of the event, incident, experience, or outcome; 
An explanation of the basis for determining that the event, incident, experience, or outcome represents 
an UP; A description of any changes to the protocol or other corrective actions that have been taken or 
are proposed in response to the UP.  The IND sponsor will make an assessment of whether the event 
constitutes an unanticipated problem posing risks to subjects or others (UP). This assessment will be 
provided to the Emory University IRB.  If the Emory IRB determines an event is a UP it will notify the 
appropriate regulatory agencies and institutional officials. 
The Data and Safety Monitoring Committee (DSMC) of the Winship Cancer Institute of Emory 
University will oversee the conduct of this study. This committee will review all pertinent aspects of the 
study conduct including patient safety, compliance with protocol, data collection, and efficacy. 
The DSMC will review the charts of 10% of patients enrolled to the study and two of the first 5 patients 
entered to the study. High-risk studies will be reviewed every 6 months. The committee reserves the right 
to conduct additional audits, if necessary, at any time-point. The Principal Investigator is responsible for 
notifying the DSMC about the accrual of patients when the first 5 have been entered to the study.
The charter for the Winship DSMC is available upon request to the investigator or other study-related 
personnel.
As with our ongoing clinical trial, for the current proposal, we will adhere strictly to Winship’s Data 
Safety 
Monitoring 
Plan 
which 
is 
provided 
in 
detail 
at 
the 
following 
link: 
https://winshipcancer.emory.edu/research/clinical-trials-office/data-and-safety-monitoring-
committee.html
Data Safety Monitoring Board: Note that our proposed trial is an early phase clinical trial that will be 
conducted completely within the Emory system, so a formal and independent Data Safety Monitoring 
Board (DSMB) [which is required for multi-site studies or Phase III trials] is not required for our 
proposal. As described above, the DSMC of Winship Cancer Institute of Emory University will oversee 
the conduct of our study. 
Fidelity to Protocol and Data Integrity:
Clinical trial performance and fidelity to the protocol will be monitored by the DSMC of Winship Cancer 
Institute of Emory University. The integrity of the data will be maintained by rigorous peer-review 
internally by all the clinical co-investigators in Radiation Oncology, Radiology/Nuclear Medicine, 
Surgical Oncology, and Medical Oncology. 
Provisions to Protect the Privacy Interest of Participants
To maintain patient confidentiality, medical records will be accessed only by IRB-approved study 
personnel (e.g. CRC). A partial HIPAA waiver will be obtained to allow screening of provider schedules 
for the identification of potentially eligible research subjects. Upon medical record review and 
identification of a potentially eligible research subject, the patient's full name, MRN, EMPI, and full dates 
(e.g., DOB, procedure dates, admission dates, etc.) will be stored on a screening log and used by study 
coordinators for the subsequent study activities. The screening log will be kept on the HIPAA compliant 
shared folder and will be accessible only to limited IRB-approved study personnel (e.g., CRC). Sensitive 
data will always be stored on the HIPAA compliant shared folder and will never be stored on local or 
portable drives that are not encrypted per Emory IS standards.

Protocol Title:   Strategy to Reduce Bladder Activity with rhPSMA 7.3: Comparison of 18F-rhPSMA 
7.3 PET/CT with and without Furosemide in Biochemical Recurrence of Prostate Cancer
Page 27 of 38
Protocol Version: Version 6: JUN/6/2024
Each study participant will be assigned a unique study identification (ID) number at the time that 
informed consent is given. Personal identifying information and study data, including the unique study 
ID, will be entered in the Microsoft Database that will be kept on the HIPAA compliant shared folder 
accessible to approved study personnel only. Only de-identified data will be shared with those outside 
the study team to ensure adequate protection of sensitive data.
Study identifiers will be kept indefinitely. 
To maintain participant confidentiality, no identifying information about any of the study participants 
will be published. Any data published (including demographic information about the study sample as a 
whole) will be in aggregate/summary form only. 
11.1
Statistical consideration section: 
 
The objective of this early phase study is to determine if administering 20mg furosemide IV at the 
time of radiotracer injection significantly reduces bladder activity compared with the same patient 
scanned without furosemide as control.
Sample size determination
We will image 20 patients with biochemical recurrence of prostate cancer post-prostatectomy for this 
study.  Based on prior observation, we assume an SUV mean of 9.2 (SD=11.1) in those receiving 20mg 
furosemide IV at the time of radiotracer injection, and an SUV mean of 2.6 (SD=1.0) in those not 
receiving furosemide (White Paper Prepared for Syncona: Evaluation of 18F-rhPSMA7, Unpublished).  
Assuming a correlation between paired measurements of 0.5 which results in a standard deviation of 
change in SUV mean of approximately 10, we have 80% power to detect that change in SUV mean (9.2 
vs. 2.6) with 20 patients, assuming a Type I error of 0.05, using a paired t-test.  The sample size was 
calculated using PASS 2020 v20.0.3.
Populations for analyses
Efficacy set: All patients administered both 20mg furosemide IV at the time of radiotracer injection and 
without furosemide.
Safety set: All patients receive a dose of the radiotracer with each study.
Statistical analyses:
General Approach
Continuous variables will be summarized using mean, median, interquartile range, standard deviation, 
and min/max.  Categorical variables will be summarized using frequencies and percentages.  All tests 
will be two-sided with an alpha level of 0.05, unless otherwise noted.  Testing assumptions will be 

Protocol Title:   Strategy to Reduce Bladder Activity with rhPSMA 7.3: Comparison of 18F-rhPSMA 
7.3 PET/CT with and without Furosemide in Biochemical Recurrence of Prostate Cancer
Page 28 of 38
Protocol Version: Version 6: JUN/6/2024
assessed and verified.  Statistical analysis will be conducted using SAS 9.4 (SAS Institute Inc., Cary, 
NC).
Analysis of the Primary Efficacy Endpoint
Change in bladder SUV mean: The primary endpoint is change in bladder activity, as measured by 
bladder SUV mean, between administration of 20mg furosemide IV at the time of radiotracer injection 
and without furosemide.  Change in bladder SUV mean will be assessed using a paired t-test, or using a 
non-parametric equivalent such as a Wilcoxon signed rank test.  Descriptively, change in bladder SUV 
mean will be reported for those administered 20mg furosemide IV at the time of radiotracer injection 
first (Group A), and those administered 20mg furosemide IV at the time of radiotracer injection second 
(Group B).
Analysis of the Secondary Endpoints:
Bladder and renal activity: Change in bladder and renal activity, as measured by bladder SUV max, 
bladder volume, and renal SUV mean/max, between administration of 20mg furosemide IV at the 
time of radiotracer injection and without furosemide will be assessed using paired t-tests, or using 
non-parametric equivalents such as a Wilcoxon signed rank tests.  Descriptively, bladder and renal 
activity will be reported for those administered 20mg furosemide IV at the time of radiotracer 
injection first (Group A), and those administered 20mg furosemide IV at the time of radiotracer 
injection second (Group B).
Recurrent disease rate: Recurrent disease is defined as presence of unequivocal soft tissue 
radiotracer uptake that is characteristic of malignancy in the prostate bed and/or surrounding soft 
tissues and within pelvic lymph nodes.  Recurrent disease rates will be compared (furosemide vs. 
non-furosemide 18F-rhPSMA-7.3 PET scans using McNemar’s tests.  Rates will be reported, along 
with 95% exact confidence intervals using the Clopper-Pearson method.  Descriptively, recurrent 
disease rate will be reported for those administered 20mg furosemide IV at the time of radiotracer 
injection first (Group A), and those administered 20mg furosemide IV at the time of radiotracer 
injection second (Group B).
Confidence score: The readers’ confidence in identifying prostate bed, pelvic and retroperitoneal 
nodal disease and other recurrence on 18F-rhPSMA-7.3 PET/CT with furosemide compared with 
the 18F-rhPSMA-7.3 PET/CT without furosemide will be scored using a 5-point Likert scale.  This 
analysis will be descriptive, with summary statistics reported with and without furosemide.
Safety Analyses: Not applicable. 
Baseline Descriptive Statistics
Patient characteristics will be summarized descriptively, using mean, median, interquartile range, 
min/max, and standard deviation for continuous variables, and using frequencies and percentages 
for categorical variables.
Interim Analysis: N/A

Protocol Title:   Strategy to Reduce Bladder Activity with rhPSMA 7.3: Comparison of 18F-rhPSMA 
7.3 PET/CT with and without Furosemide in Biochemical Recurrence of Prostate Cancer
Page 29 of 38
Protocol Version: Version 6: JUN/6/2024
16.2 Data/specimens:
Patients will be monitored by the technologists and/or study nurse before and after 
the studies for any adverse events/reactions. They will be given contact phone 
numbers to call if they experience any problems (i.e., problems with the IV site, any 
allergic reaction symptoms). Basic monitoring of adverse events during the 18F-
rhPSMA-7.3 PET visit will be performed. This will consist of direct observation by 
our study staff during the visit with documentation of any adverse events or lack 
thereof in the electronic medical record. 
The Data and Safety Monitoring Committee (DSMC) of the Winship Cancer 
Institute of Emory University will oversee the conduct of this study. This committee 
will review all pertinent aspects of the study conduct including patient safety, 
compliance with protocol, data collection, and efficacy. 
The DSMC will review the charts of 10% of patients enrolled to the study and two of 
the first 5 patients entered to the study. High-risk studies will be reviewed every 6 
months. The committee reserves the right to conduct additional audits, if necessary, 
at any time-point. The Principal Investigator is responsible for notifying the DSMC 
about the accrual of patients when the first 5 have been entered to the study.
The charter for the Winship DSMC is available upon request to the investigator or 
other study-related personnel.
As with our ongoing clinical trial, for the current proposal, we will adhere strictly to 
Winship’s Data Safety Monitoring Plan which is provided in detail at the following 
link: https://winshipcancer.emory.edu/research/clinical-trials-office/data-and-safety-
monitoring-committee.html
Data Safety Monitoring Board: Note that our proposed trial is an early phase clinical 
trial that will be conducted completely within the Emory system, so a formal and 
independent Data Safety Monitoring Board (DSMB) [which is required for multi-site 
studies or Phase III trials] is not required for our proposal. As described above, the 
DSMC of Winship Cancer Institute of Emory University will oversee the conduct of 
our study. 
Fidelity to Protocol and Data Integrity:
Clinical trial performance and fidelity to the protocol will be monitored by the 
DSMC of Winship Cancer Institute of Emory University. The integrity of the data 
will be maintained by rigorous peer-review internally by all the clinical co-
investigators in Radiation Oncology, Radiology/Nuclear Medicine, Surgical 
Oncology, and Medical Oncology.

Protocol Title:   Strategy to Reduce Bladder Activity with rhPSMA 7.3: Comparison of 18F-rhPSMA 
7.3 PET/CT with and without Furosemide in Biochemical Recurrence of Prostate Cancer
Page 30 of 38
Protocol Version: Version 6: JUN/6/2024
12. Provisions to Monitor the Data to Ensure the Safety of Participants
Patients will be monitored by the technologists and/or study nurse before and after the 
studies for any adverse events/reactions. They will be given contact phone numbers to 
call if they experience any problems (i.e., problems with the IV site, any allergic 
reaction symptoms). Basic monitoring of adverse events during the 18F-rhPSMA-7.3 
PET visit will be performed. This will consist of direct observation by our study staff 
during the visit with documentation of any adverse events or lack thereof in the 
electronic medical record. The physical half-life of the radiotracer is 110 minutes. 
Hence, adverse events are not expected to occur past 24 hrs after radiotracer 
administration.
Written IND safety reports will be submitted to the FDA by the IND sponsor, for 
serious, unexpected suspected adverse reactions within 15 calendar days of learning 
of its occurrence. If the event is fatal or is deemed to be life threatening, the report will 
be made within 7 calendar days.  The IND sponsor will also make an assessment of 
whether the event constitutes an unanticipated problem posing risks to subjects or 
others (UP). This assessment will be provided to the Emory University IRB, which, 
in turn will make a final determination.  If the Emory IRB determines an event is a UP 
it will notify the appropriate regulatory agencies and institutional officials.
In addition to reporting of Serious Adverse Events (SAEs) to the responsible IRB/IEC 
and Health Authority, Principal Investigator or designee will inform Blue Earth 
Diagnostics (BED) of all SAEs in connection with the Study that occur following 
receipt of rhPSMA-7.3, whether or not related to Product. 
PI or designee shall notify BED within twenty-four (24) hours of knowledge of any 
SAEs.  SAE reports to BED must be recorded and faxed or scanned and emailed to: 
Bracco Diagnostics Inc. Drug Safety Unit 
E mail:  Drugsafetyus@BlueEarthDx.com  
Fax:   +1-609-514-2522
To the extent permitted by federal law, additional and further requested information 
(follow-up or corrections to the original case) will be detailed and faxed/emailed to 
the same address and will include the following minimum information: The name and 
contact information of the reporter, the name of the study drug(s), a description of the 
reported SAE, with the patient identified by one or more of the following (patient 
initials/code, patient number  age, sex), an investigator assessment of study drug 
causality, and any additional data customarily accompanying such reports which 
would aid the review and causality assessment of the case including but not limited to 
the date of onset, severity, the time from administration of study drug(s) to start of the 
event, the duration and outcome of the event, any possible etiology for the event, and 
the final diagnosis or syndrome, if known.

Protocol Title:   Strategy to Reduce Bladder Activity with rhPSMA 7.3: Comparison of 18F-rhPSMA 
7.3 PET/CT with and without Furosemide in Biochemical Recurrence of Prostate Cancer
Page 31 of 38
Protocol Version: Version 6: JUN/6/2024
Definition of unanticipated problems (UP) and reporting requirements
The Office for Human Research Protections (OHRP) considers unanticipated 
problems involving risks to participants or others to include, in general, any incident, 
experience, or an outcome that meets all the following criteria:  Unexpected in terms 
of nature, severity, or frequency given (a) the research procedures that are described 
in the protocol-related documents, such as the IRB-approved research protocol and 
informed consent document; and (b) the characteristics of the participant population 
being studied; Related or possibly related to participation in the research (“possibly 
related” means there is a reasonable possibility that the incident, experience, or 
outcome may have been caused by the procedures involved in the research); and 
suggests that the research places participants or others at a greater risk of harm 
(including physical, psychological, economic, or social harm) than was previously 
known or recognized.  This study will use the OHRP definition of unanticipated 
problems. Incidents or events that meet the OHRP criteria for UPs require the creation 
and completion of a UP report form. It is the site investigator’s responsibility to report 
UPs to their IRB and to the DCC/study sponsor. The UP report will include the 
following information:  Protocol identifying information: protocol title and number, 
PI’s name, and the IRB project number; A detailed description of the event, incident, 
experience, or outcome; An explanation of the basis for determining that the event, 
incident, experience, or outcome represents an UP; A description of any changes to 
the protocol or other corrective actions that have been taken or are proposed in 
response to the UP.  The IND sponsor will make an assessment of whether the event 
constitutes an unanticipated problem posing risks to subjects or others (UP). This 
assessment will be provided to the Emory University IRB.  If the Emory IRB 
determines an event is a UP it will notify the appropriate regulatory agencies and 
institutional officials. 
The Data and Safety Monitoring Committee (DSMC) of the Winship Cancer Institute 
of Emory University will oversee the conduct of this study. This committee will 
review all pertinent aspects of the study conduct including patient safety, compliance 
with protocol, data collection, and efficacy. 
The DSMC will review the charts of 10% of patients enrolled to the study and two of 
the first 5 patients entered to the study. High-risk studies will be reviewed every 6 
months. The committee reserves the right to conduct additional audits, if necessary, at 
any time-point. The Principal Investigator is responsible for notifying the DSMC 
about the accrual of patients when the first 5 have been entered to the study.
The charter for the Winship DSMC is available upon request to the investigator or 
other study-related personnel.
As with our ongoing clinical trial, for the current proposal, we will adhere strictly to 
Winship’s Data Safety Monitoring Plan which is provided in detail at the following 
link: https://winshipcancer.emory.edu/research/clinical-trials-office/data-and-safety-
monitoring-committee.html

Protocol Title:   Strategy to Reduce Bladder Activity with rhPSMA 7.3: Comparison of 18F-rhPSMA 
7.3 PET/CT with and without Furosemide in Biochemical Recurrence of Prostate Cancer
Page 32 of 38
Protocol Version: Version 6: JUN/6/2024
Data Safety Monitoring Board: Note that our proposed trial is an early phase clinical 
trial that will be conducted completely within the Emory system, so a formal and 
independent Data Safety Monitoring Board (DSMB) [which is required for multi-site 
studies or Phase III trials] is not required for our proposal. As described above, the 
DSMC of Winship Cancer Institute of Emory University will oversee the conduct of 
our study. 
Fidelity to Protocol and Data Integrity:
Clinical trial performance and fidelity to the protocol will be monitored by the DSMC of Winship Cancer 
Institute of Emory University. The integrity of the data will be maintained by rigorous peer-review 
internally by all the clinical co-investigators in Radiation Oncology, Radiology/Nuclear Medicine, 
Surgical Oncology, and Medical Oncology.
13.   Provisions to Protect the Privacy Interests of Participants
To maintain patient confidentiality, medical records will be accessed only by IRB-
approved study personnel (e.g. CRC). A partial HIPAA waiver will be obtained to allow 
screening of provider schedules for the identification of potentially eligible research 
subjects. Upon medical record review and identification of a potentially eligible research 
subject, the patient's full name, MRN, EMPI, and full dates (e.g., DOB, procedure dates, 
admission dates, etc.) will be stored on a screening log and used by study coordinators 
for the subsequent study activities. The screening log will be kept on the HIPAA 
compliant shared folder and will be accessible only to limited IRB-approved study 
personnel (e.g., CRC). Sensitive data will always be stored on the HIPAA compliant 
shared folder and will never be stored on local or portable drives that are not encrypted 
per Emory IS standards.
Each study participant will be assigned a unique study identification (ID) number at the 
time that informed consent is given. Personal identifying information and study data, 
including the unique study ID, will be entered in the Microsoft Database that will be 
kept on the HIPAA compliant shared folder accessible to approved study personnel 
only. Only de-identified data will be shared with those outside the study team to ensure 
adequate protection of sensitive data.
Study identifiers will be kept indefinitely. 
To maintain participant confidentiality, no identifying information about any of the study 
participants will be published. Any data published (including demographic information about 
the study sample as a whole) will be in aggregate/summary form only.

Protocol Title:   Strategy to Reduce Bladder Activity with rhPSMA 7.3: Comparison of 18F-rhPSMA 
7.3 PET/CT with and without Furosemide in Biochemical Recurrence of Prostate Cancer
Page 33 of 38
Protocol Version: Version 6: JUN/6/2024
14.    Economic Burden to Participants
There will be no cost for the patients to participate in this study.
15.   Consent Process
Informed consent is required prior to participation in the study. Patients will sign the written 
informed consent, if possible, at the time of enrollment. The patient will be sent a copy of the 
consent form prior to enrollment. The consent process will take place at the radiation oncology, 
oncology, or nuclear radiology clinics at Emory Healthcare. The consent will be obtained by 
one of the investigators or those who have been given the authority in the DOA log. The 
consent will take up to 30 minutes to explain to the patients and patients will be given time to 
ask questions. Special precautions will be taken to not influence patient’s decision to take part 
in the study.
e-Consent
The PI and/or delegated co-I and/or delegated study team will have the option to consent the 
participants electronically using Zoom. The PI and/or delegated co-I and/or delegated study 
team will conduct the consent discussion via phone or Zoom. A copy of the study Emory IRB 
approved consent form will be sent to the participants to be signed using CFR Part 11 
Compliant DocuSign.  The PI and/or delegated co-I and/or delegated study team will ask the 
participants a security question to confirm their identity (security question: What was your 
mother's maiden name?). The participants will receive a copy of the electronically signed study 
consent form on their first research visit. 
Non-English-Speaking Participants  
Non-English-speaking participants may be considered for enrollment in this trial subjects with 
limited English proficiency (LEP) may be enrolled and study team members will use Emory IRB 
approved short forms to conduct the consent process. The subject will date and sign the consent 
form. The subject will receive a copy of the dated and signed consent form                                                       
16. Setting
All patients will be recruited from the radiation oncology unit and other oncology units under Emory 
Healthcare
17.   Resources Available
PET/CT scanners: PET/CT will be acquired on a state-of-the-art GE Discovery 690 TOF 
PET-CT scanner at Emory University Hospital or similar device.
Radiotracer: The study will be performed under IND #162587 held by Dr. David Schuster.
Time allotment: PET/CT studies will be performed per protocol described above. The 
studies will be read by investigators as detailed above, Time taken for interpretation may 
vary per study. 

Protocol Title:   Strategy to Reduce Bladder Activity with rhPSMA 7.3: Comparison of 18F-rhPSMA 
7.3 PET/CT with and without Furosemide in Biochemical Recurrence of Prostate Cancer
Page 34 of 38
Protocol Version: Version 6: JUN/6/2024
Training: All study personnel will be adequately trained regarding the details of the protocol prior to 
study initiation.
18.   References
1.
Cookson MS, Aus G, Burnett AL, et al. Variation in the definition of biochemical recurrence in 
patients treated for localized prostate cancer: the American Urological Association Prostate 
Guidelines for Localized Prostate Cancer Update Panel report and recommendations for a 
standard in the reporting of surgical outcomes. J Urol 2007;177:540-545
2.
Cornford P, Bellmunt J, Bolla M, et al. EAU-ESTRO-SIOG Guidelines on Prostate Cancer. Part II: 
Treatment of Relapsing, Metastatic, and Castration-Resistant Prostate Cancer. Eur Urol 
2017;71:630-642
3.
Schuster DM, Nieh PT, Jani AB, et al. Anti-3-[(18)F]FACBC positron emission tomography-
computerized tomography and (111)In-capromab pendetide single photon emission 
computerized tomography-computerized tomography for recurrent prostate carcinoma: 
results of a prospective clinical trial. J Urol 2014;191:1446-1453
4.
Jani AB, Schreibmann E, Goyal S, et al. (18)F-fluciclovine-PET/CT imaging versus conventional 
imaging alone to guide postprostatectomy salvage radiotherapy for prostate cancer (EMPIRE-
1): a single centre, open-label, phase 2/3 randomised controlled trial. Lancet 2021;397:1895-
1904
5.
Schuster DM, Nanni C, Fanti S, et al. Anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid: 
physiologic uptake patterns, incidental findings, and variants that may simulate disease. 
Journal of nuclear medicine : official publication, Society of Nuclear Medicine 2014;55:1986-
1992
6.
Bostwick DG, Pacelli A, Blute M, Roche P, Murphy GP. Prostate specific membrane antigen 
expression in prostatic intraepithelial neoplasia and adenocarcinoma: a study of 184 cases. 
Cancer 1998;82:2256-2261
7.
Rauscher I, Krönke M, König M, et al. Matched-Pair Comparison of (68)Ga-PSMA-11 PET/CT 
and (18)F-PSMA-1007 PET/CT: Frequency of Pitfalls and Detection Efficacy in Biochemical 
Recurrence After Radical Prostatectomy. Journal of nuclear medicine : official publication, 
Society of Nuclear Medicine 2020;61:51-57
8.
Giesel FL, Hadaschik B, Cardinale J, et al. F-18 labelled PSMA-1007: biodistribution, radiation 
dosimetry and histopathological validation of tumor lesions in prostate cancer patients. Eur J 
Nucl Med Mol Imaging 2017;44:678-688
9.
Oh SW, Wurzer A, Teoh EJ, et al. Quantitative and Qualitative Analyses of Biodistribution and 
PET Image Quality of a Novel Radiohybrid PSMA, (18)F-rhPSMA-7, in Patients with Prostate 

Protocol Title:   Strategy to Reduce Bladder Activity with rhPSMA 7.3: Comparison of 18F-rhPSMA 
7.3 PET/CT with and without Furosemide in Biochemical Recurrence of Prostate Cancer
Page 35 of 38
Protocol Version: Version 6: JUN/6/2024
Cancer. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 
2020;61:702-709
10.
Tolvanen T, Kalliokoski KK, Malaspina S, et al. Safety, biodistribution and radiation dosimetry of 
(18)F-rhPSMA-7.3 in healthy adult volunteers. Journal of nuclear medicine : official publication, 
Society of Nuclear Medicine 2020
11.
Eiber M, Kroenke M, Wurzer A, et al. (18)F-rhPSMA-7 PET for the Detection of Biochemical 
Recurrence of Prostate Cancer After Radical Prostatectomy. Journal of nuclear medicine : 
official publication, Society of Nuclear Medicine 2020;61:696-701
12.
Wurzer A, Parzinger M, Konrad M, et al. Preclinical comparison of four [(18)F, (nat)Ga]rhPSMA-
7 isomers: influence of the stereoconfiguration on pharmacokinetics. EJNMMI Res 
2020;10:149
13.
Rauscher I, Karimzadeh A, Schiller K, et al. Detection efficacy of (18)F-rhPSMA-7.3 PET/CT and 
impact on patient management in patients with biochemical recurrence of prostate cancer 
after radical prostatectomy and prior to potential salvage treatment. Journal of nuclear 
medicine : official publication, Society of Nuclear Medicine 2021;62:1719-1726
14.
Uprimny C, Bayerschmidt S, Kroiss AS, et al. Impact of forced diuresis with furosemide and 
hydration on the halo artefact and intensity of tracer accumulation in the urinary bladder and 
kidneys on [68Ga]Ga-PSMA-11-PET/CT in the evaluation of prostate cancer patients. European 
Journal of Nuclear Medicine and Molecular Imaging 2021;48:123-133
15.
Alberts I, Huenermund JN, Sachpekidis C, et al. Combination of forced diuresis with additional 
late imaging in (68)Ga-PSMA-11 PET/CT - effects on lesion visibility and radiotracer uptake. 
Journal of nuclear medicine : official publication, Society of Nuclear Medicine 2021
16.
Fendler WP, Eiber M, Beheshti M, et al. 68Ga-PSMA PET/CT: Joint EANM and SNMMI 
procedure guideline for prostate cancer imaging: version 1.0. European Journal of Nuclear 
Medicine and Molecular Imaging 2017;44:1014-1024
17.
Schuster D. Detection rate of 18F-rhPSMA-7.3 PET in patients with suspected prostate cancer 
recurrence: Results from a phase 3, prospective, multicenter study (SPOTLIGHT). Journal of 
Clinical Oncology 2022;40:9-9
18.
Uprimny C, Bayerschmidt S, Kroiss AS, et al. Early Injection of Furosemide Increases Detection 
Rate of Local Recurrence in Prostate Cancer Patients with Biochemical Recurrence Referred for 
(68)Ga-PSMA-11 PET/CT. J Nucl Med 2021;62:1550-1557

Protocol Title:   Strategy to Reduce Bladder Activity with rhPSMA 7.3: Comparison of 18F-rhPSMA 
7.3 PET/CT with and without Furosemide in Biochemical Recurrence of Prostate Cancer
Page 36 of 38
Protocol Version: Version 6: JUN/6/2024
APPENDIX A
PERFORMANCE STATUS CRITERIA
ECOG Performance Status Scale
Karnofsky Performance Scale
Grade
Descriptions
Percent
Description
100
Normal, no complaints, no evidence 
of disease.
0
Normal activity.  Fully active, able 
to 
carry 
on 
all 
pre-disease 
performance without restriction.
90
Able to carry on normal activity; 
minor signs or symptoms of disease.
80
Normal activity with effort; some 
signs or symptoms of disease.
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).
70
Cares for self, unable to carry on 
normal activity or to do active work.
60
Requires occasional assistance, but is 
able to care for most of his/her needs.
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.
50
Requires considerable assistance and 
frequent medical care.
40
Disabled, requires special care and 
assistance.
3
In bed >50% of the time.  Capable 
of only limited self-care, confined 
to bed or chair more than 50% of 
waking hours.
30
Severely disabled, hospitalization 
indicated.  Death not imminent.
20
Very sick, hospitalization indicated. 
Death not imminent.
4
100% bedridden.  Completely 
disabled.  Cannot carry on any self-
care.  Totally confined to bed or 
chair.
10
Moribund, 
fatal 
processes 
progressing rapidly.
5
Dead.
0
Dead.
As published in Am. J. Clin. Oncol.:  Oken, M.M., Creech, R.H., Tormey, D.C., Horton, J., Davis, 
T.E., McFadden, E.T., Carbone, P.P.: Toxicity And Response Criteria Of The Eastern Cooperative 
Oncology Group. Am J Clin Oncol 5:649-655, 1982. The Eastern Cooperative Oncology Group, 
Robert Comis M.D., Group Chair

Protocol Title:   Strategy to Reduce Bladder Activity with rhPSMA 7.3: Comparison of 18F-rhPSMA 
7.3 PET/CT with and without Furosemide in Biochemical Recurrence of Prostate Cancer
Page 37 of 38
Protocol Version: Version 6: JUN/6/2024

Protocol Title:   Strategy to Reduce Bladder Activity with rhPSMA 7.3: Comparison of 18F-rhPSMA 
7.3 PET/CT with and without Furosemide in Biochemical Recurrence of Prostate Cancer
Page 38 of 38
Protocol Version: Version 6: JUN/6/2024
APPENDIX C   Abbreviations and definition of terms
Abbreviation or special 
term
Explanation
AEs
Adverse effects
ADT
Androgen-deprivation therapy
CRC
Clinical Research Coordinator
CRF
Case Report Form
CT
Computed tomography
CTCAE
Common Terminology Criteria for Adverse Event
CTEP
Cancer Therapy Evaluation Program
DSMC
Data and Safety Monitoring Committee
DSMP
Data Safety and Monitoring Plan
DSUR
Development Safety Update Report
EANM
European Association of Nuclear Medicine
F-18
Fluorine-18 
FDA
Food and Drug Administration
18Ga-PSMA
Gallium-68 prostate-specific membrane antigen
HIPAA
Health Insurance Portability Accountability Act
ICF
Informed consent form
IND
Investigational New Drug
IRB
Institutional Review Board
IV
Intravenous
MBq
Mega Becquerel
mGy
MilliGray
MRI
Magnetic resonance imaging
mSv
milliSievert
MTV
Metabolic tumor volume
NCCN
National Comprehensive Cancer Network
NCI
National Cancer Institute
PET/CT
Positron emission tomography/ computed tomography
rhPSMA
Radiohybrid prostate-specific membrane antigen
PSA
Prostate-specific antigen
RP
Radical prostatectomy
SAEs
Severe adverse effects
SNMMI
Society of Nuclear Medicine and Molecular Imaging
SUV max
Maximum standardized uptake value
TLA
Total lesion activity