Evaluation of PSMA Antagonist Produced by Two Different Methods

Study Overview
=================
Brief Summary
-----------------
Patients with metastatic prostate cancer will undergo two protocol 68Ga-PET scans within 24-48 hours with 68Ga-PSMA-cyclotron and 68Ga-PSMA-generator radiotracers. The goal of the study is to evaluate repeatability and equivalence across the different 68Ga-PSMA production methods. This research study is being conducted to assess whether the PET/CT imaging results, as generated from the two different 68Ga production methods, are equivalent.

Detailed Description
-----------------
Patients with metastatic prostate adenocarcinoma will be enrolled in the study and will undergo two 68Ga-Prostate Specific Membrane Antigen- Positron Emission Tomography (PSMA-PET) scans within 24-48 hours. The difference between the two scans is that the radiotracer used in each scan will be produced with a different method (68Ga-PSMA-cyclotron and 68Ga-PSMA-generator produced). The first scan will occur after a baseline clinical evaluation, which will include a history, physical, and baseline lab draw. After each scan, blood draws will be obtained. The purpose of this study is to evaluate equivalence of two processes to create 68Ga-HBED-PSMA and compare dosimetry, biodistribution and whole body excretion/ metabolism. Furthermore, the research team will perform dynamic analysis of the PET scans to investigate repeatability of whole-body 68Ga-PSMA-generator Ki Patlak imaging against that of conventional whole-body 68Ga-PSMA- SUV imaging and evaluate equivalence of whole-body 68Ga-PSMA Ki Patlak imaging between the two processes to create 68Ga-HBED-PSMA (68GA-PSMA-cyclotron vs. 68Ga-PSMA-generator). Patients will afterwards receive standard of care treatment and follow up imaging.

Official Title
-----------------
Evaluation of a 68Ga Small Molecule PSMA Antagonist Produced by Two Different Methods

Conditions
-----------------
Metastatic Prostate Adenocarcinoma

Intervention / Treatment
-----------------
* Drug: 68Ga-PSMA-generator vs. 68Ga-PSMA-cyclotron


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects must meet all of the following criteria to be enrolled in this study: Aged 21 years or older and below 80 years of age Signed written informed consent and willingness to comply with protocol requirements Histologically confirmed diagnosis of metastatic prostate cancer Staging imaging exam confirming metastatic disease, e.g. total body MRI, or CT chest/abdomen/pelvis, 99mTc bone scan, NaF PET Exclusion Criteria: Laboratory values: Serum creatinine >2.5 mg/dL AST (SGOT) >2.5x ULN Bilirubin (total) >1.5x ULN Serum calcium >11 mg/dL Presence of any other co-existing condition which, in the judgment of the investigator, might increase the risk to the subject. Presence of serious systemic illness, including: uncontrolled inter-current infection, uncontrolled malignancy, significant renal disease, or psychiatric/social situations, which might limit compliance with study requirements. Other severe acute or chronic medical condition(s) or laboratory abnormality(ies) that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and in the judgment of the investigator, would make the patient inappropriate for entry into this study. Inability to lay on the scanner table for the required period of time, e.g., due to bone pain or claustrophobia.

Ages Eligible for Study
-----------------
Minimum Age: 21 Years
Maximum Age: 100 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 68Ga-PSMA-generator vs. 68Ga-PSMA-cyclotron<br>Patients with metastatic prostate cancer will undergo two protocol 68Ga-PET scans within 24-48 hours with 68Ga-PSMA-cyclotron and 68Ga-PSMA-generator radiotracers. | Drug: 68Ga-PSMA-generator vs. 68Ga-PSMA-cyclotron<br>* 68Ga-PSMA-generator vs. 68Ga-PSMA-cyclotron; single dose each, approximately 100-300 mBq.<br>* Other names: Prostate specific membrane antigen imaging (PSMA);|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate Equivalence Between 68GA-PSMA-cyclotron and 68Ga-PSMA-generator Across Varying Pathologic Lesions | Single score Intraclass Correlation Coefficient (ICC) was calculated as an index for reliability between 68GA-PSMA-cyclotron versus 68Ga-PSMA-generator across varying pathologic lesions. The ICC, based on a one-way random effects model was used to assess reliability. The ICC ratios in this data shows the top five lesions with the greatest PSMA uptake (SUV) in each patient. This is a measure of the variance of interest (for the patient's lesion) over the total variance (from all data points for that particular lesion of interest). Repeatability was evaluated by calculating the variance among group means of the SUVmean and SUVmax of each reference and lesion over the sum of the group-level and datalevel (residual) variance. The lesions reported in this analysis range from the SUV of reference organs to the average SUV of a metastatic deposit. These scans were also performed within 48 hours of each other to limit heterogeneity that may correspond to disease progression or PSMA avidity. | 2 study visits between 24 to 48 hours apart | 
| Evaluate Equivalence Between 68GA-PSMA-cyclotron and 68Ga-PSMA-generator Across Varying Average SUV Max-pathologic Regions | Single score intraclass correlation coefficient (ICC) was calculated as an index for reliability between 68GA-PSMA-cyclotron versus 68Ga-PSMA-generator across varying average SUV Max-pathologic regions The ICC ratios in this data provides a general performance review of uptake in both pathological lesions and reference lesions, specifically the average SUVmax of bone metastases, lymph nodes, salivary glands, and the spleen. | 2 study visits between 24 to 48 hours apart | 
| ICC Between Generator PSMA Scan vs Cyclotron PSMA Scan: Total Lesion Average SUVMax | Repeatability was evaluated by calculating the variance among group means of the SUVmean and SUVmax of each reference and lesion over the sum of the group-level and datalevel (residual) variance. The intraclass correlation coefficient (ICC), based on a one-way random effects model (i.e., assumes subjects are randomly selected from the larger population), was used to assess reliability between generator and cyclotron scanning methods. BlandAltman analysis evaluated the agreement between the two scanning methods. Confidence levels of 95% were estimated to assess precision of the obtained estimates. All analyses were performed in R Version 4.0.5 (R Foundation for Statistical Computing, Vienna, Austria). | 2 study visits between 24 to 48 hours apart | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate Equivalence Between 68GA-PSMA-cyclotron and 68Ga-PSMA-generator Across Varying Max SUV -Pathologic Regions | Single score intraclass correlation coefficient (ICC) was calculated as an index for reliability between 68GA-PSMA-cyclotron versus 68Ga-PSMA-generator across varying Max SUV -pathologic regions Repeatability was evaluated by calculating the variance among group means of the SUVmean and SUVmax of each reference and lesion over the sum of the group-level and datalevel (residual) variance. The intraclass correlation coefficient (ICC), based on a one-way random effects model (i.e., assumes subjects are randomly selected from the larger population), was used to assess reliability between generator and cyclotron scanning methods. BlandAltman analysis evaluated the agreement between the two scanning methods. Confidence levels of 95% were estimated to assess precision of the obtained estimates. All analyses were performed in R Version 4.0.5 (R Foundation for Statistical Computing, Vienna, Austria). | 2 study visits between 24 to 48 hours apart | 
| Compare Bio-Distribution Between 68GA-PSMA-cyclotron vs. 68Ga-PSMA-generator | The biodistribution of 68GA-PSMA-cyclotron versus 68Ga-PSMA-generator will be evaluated by measuring the radioactivity concentration in various organs of interest. Based on the SUVmean and SUVmax, the RC unit will be used to compare these scans. PSMA positivity was defined as having a SUV value above that of the reference blood pool, liver, and/or salivary glands when evaluating lesions as described using the PROMISE criteria15. Quantitative analysis reviewed the SUVmax and SUVmean of the parotid gland, liver, and aortic arch (blood pool), as well as the SUVmax and SUVmean of suspected metastatic lesions. The same ROIs were evaluated on both scans for each respective patients. | 2 study visits between 24 to 48 hours apart | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Prostate Cancer