Phase I Dose-escalation Study of Fractionated 177Lu-PSMA-617 for Progressive Metastatic CRPC

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. ECOG performance status of 0-2 4. 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. 5. Have previously been treated with at least one of the following: * Androgen receptor signaling inhibitor (such as enzalutamide) * CYP 17 inhibitor (such as abiraterone acetate) 6. Have previously received taxane chemotherapy, been determined to be ineligible for taxane chemotherapy by their physician, or refused taxane chemotherapy. 7. Age \> 18 years 8. Patients must have normal organ and marrow function as defined below: * Absolute neutrophil count \>2,000 cells/mm3 * Hemoglobin ≥9 g/dL (independent of transfusion and/or growth factors within 1 month prior to registration) * Platelet count \>150,000 x 109/uL (independent of transfusion and/or growth factors within 3 months prior to randomization) * Serum creatinine \<1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥ 60 mL/min/1.73 m2 by Cockcroft-Gault * Serum total bilirubin \<1.5 x ULN (unless due to Gilbert's syndrome in which case direct bilirubin must be normal * Serum AST and ALT \<1.5 x ULN 9. Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: 1. Use of investigational drugs or implantation of investigational medical device ≤4 weeks of Cycle 1, Day 1 or current enrollment in investigational drug or device study 2. Prior systemic beta-emitting bone-seeking radioisotopes 3. Brain metastases or leptomeningeal disease 4. History of deep vein thrombosis and/or pulmonary embolus within 1 month of study entry 5. Other serious illness(es) involving the cardiac, respiratory, CNS, renal, hepatic or hematological organ systems which might preclude completion of this study or interfere with determination of causality of any adverse effects experienced in this study 6. Radiation therapy for treatment of PCa ≤4 weeks of Day 1 Cycle 1 7. Patients on stable dose of bisphosphonates or denosumab, which have been started no less than 4 weeks prior to treatment start, may continue on this medication, however patients are not allowed to initiate bisphosphonate/Denosumab therapy during the DLT-assessment period of the study. 8. Having partners of childbearing potential and not willing to use a method of birth control deemed acceptable by the principle investigator and chairperson during the study and for 1 month after last study drug administration 9. Currently active other malignancy other than non-melanoma skin cancer. Patients are considered not to have "currently active" malignancy if they have completed any necessary therapy and are considered by their physician to be at less than 30% risk of relapse. 10. Known history of known myelodysplastic syndrome