Mechanisms of Resistance to PSMA Radioligand Therapy

PRIMARY OBJECTIVES: I. To determine the relationship between whole body tumor absorbed dose and response Lutetium based prostate-specific membrane antigen-targeted radioligand therapy (177Lu-PSMA-RLT). II. To determine the relationship between Post-Operative Radiation Therapy Outcomes Score (PORTOS) score and response to 177Lu-PSMA-RLT. III. To determine the relative importance of radiation dose (whole body tumor absorbed dose) and radiation sensitivity (PORTOS score) as a marker of response to 177Lu-PSMA-RLT. EXPLORATORY OBJECTIVES: I. To develop novel signature of radiation sensitivity. II. To evaluate tumor biopsies to understand mechanisms of resistance. III. To understand utility of post-cycle 4 single-photon emission computed tomography (SPECT/CT) to evaluate treatment response. Study participants will undergo a biopsy and blood draw prior to the initiation of planned therapy, as well as SPECT/CT imaging performed after the first and fourth treatments. One SPECT/CT scan will be performed 24 (+/- 6) after the first treatment, and after the fourth treatment, a 24 +/- 6-hour post-treatment SPECT/CT will be performed. Additionally, study participants may choose to undergo optional biopsy and blood draw at time of progression.