Fractionated and Multiple Dose 225Ac-J591 for Progressive mCRPC

The purpose of the initial (phase I) portion of this study is to find a dose level and administration schedule of the study drug, 225Ac-J591, that can be given without severe side effects. The purpose of the second (phase II) portion of the study is to determine the proportion of those with PSMA-positive tumors with \>50% PSA decline following 225Ac-J591 treatment in two regimens.

Inclusion Criteria: 1. Histologically or cytologically confirmed adenocarcinoma of prostate 2. Documented progressive metastatic CRPC based on Prostate Cancer Working Group 3 (PCWG3) criteria, which includes at least one of the following criteria: * PSA progression * Objective radiographic progression in soft tissue * New bone lesions 3. Have serum testosterone \< 50 ng/dL. Subjects must continue primary androgen deprivation with an LHRH/GnRH analogue (agonist/antagonist) if they have not undergone orchiectomy 4. Have previously been treated with at least one of the following in any disease state: * Androgen receptor signaling inhibitor (such as enzalutamide) * CYP 17 inhibitor (such as abiraterone acetate) 5. Have previously received taxane chemotherapy (in any disease state), been determined to be ineligible for taxane chemotherapy by their physician, or refused taxane chemotherapy. 6. Age \> 18 years 7. Patients must have normal organ and marrow function as defined below: * Absolute neutrophil count \>2,000 cells/mm3 * Hemoglobin ≥9 g/dL * Platelet count \>150,000 x 109/uL * Serum creatinine \