This single center imaging study involves one microdose of the imaging agent, followed by whole body PET imaging. Imaging data will be acquired in up to four PET studies to determine tumor and normal tissue uptake and dosimetry.~PRIMARY OBJECTIVES:~To determine the optimal time point for imaging (based on analyzing the 4 scans of all participants using 89Zr-DFO-YS5 PET post-injection. (Cohort A)~To determine the optimal antibody dose for imaging using 89Zr-DFO-YS5 PET. (Cohort B).~To determine the sensitivity of metastatic lesion detection in mCRPC using 89Zr-DFO-YS5 PET as compared with conventional imaging.(Cohorts C & D)~SECONDARY OBJECTIVES:~To determine the safety of 89Zr-DFO-YS5.~To determine average organ uptake of 89Zr-DFO-YS5 (Cohort C & D).~To descriptively report the patterns of intra-tumoral uptake of 89Zr-DFO-YS5 on whole body PET, including by site of disease, uptake by tumor type, inter-tumoral and inter-patient heterogeneity, and tumor-to-background signal (Cohorts C & D).~ARMS:~Cohort A: PET imaging data will be acquired up to four times to determine tumor and normal tissue uptake and dosimetry. The optimized scan time will be used for imaging in Cohorts B and C.~Cohort B: A dose of cold, non-radiolabeled antibody administered will be varied to determine the optimal antibody dose for image quality. The optimized antibody dose will be used in Cohort C and D. Participants will be followed for an additional 4-5 weeks after dose administration to assess for adverse events. Participants have the option to receive a repeat scan at the time of disease progression.~Cohort C: PET imaging will be acquired at the optimal time point and optimal antibody dose determined in Cohorts A & B. Participants in Cohort C have the option to receive a repeat scan at the time of disease progression.~Cohort D: PET imaging will be acquired at four time points using the antibody to enable calculation of tumor and organ dosimetry. This cohort enrolls concurrently with Cohort C.~All participants will be followed for up to 5 weeks after their first scan to assess for adverse events
CD46 is an exciting new therapeutic target in prostate cancer, with the antibody drug conjugate FOR46 under investigation in phase I clinical trials. The hypothesis of the study is that CD46 expression, measured via our novel imaging biomarker, is a characteristic feature of mCRPC, and particularly common in the most lethal forms of the disease including adenocarcinoma and Small-cell neuroendocrine carcinoma (SCNC). These data will provide crucial information about the feasibility of targeting cluster of differentiation 46 (CD46) in mCRPC, will be used guide the development of novel therapeutic and theranostic agents, to help develop treatments that improve outcomes for men with the most lethal forms of prostate cancer.