Comparison of 177Lu-PSMA-617 and 225Ac-PSMA-617

Inclusion Criteria22

• Histologically confirmed prostate adenocarcinoma.
• Willing to undergo prostatectomy with or without lymph node dissection, and candidate for prostatectomy as determined by urologic oncology.
• High-risk disease as defined as meeting 1 or more of the 3 following criteria:
• Gleason score of 4+5 disease or higher.
• Pelvic nodal metastases on PSMA PET.
• Extracapsular extension or seminal vesicle invasion on MRI.
• No evidence of distant metastatic disease as determined by PSMA PET. Nodal disease below the iliac bifurcation (clinical stage N1) is allowed.
• Maximum Standardized Uptake Value (SUVmax) in the primary tumor greater than 10 on PSMA PET using Gallium-68 (68Ga)-PSMA-11 or piflufolastat F 18 (18F-DCFPyL).
• Target tumor in the prostate measuring greater than 2 cm on MRI.
• Age ≥18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%),
• Demonstrates adequate organ function as defined below:
• Platelets ≥100,000/mcL, independent of transfusions or growth factors within 3 months of treatment start.
• Hemoglobin ≥10 g/dL, independent of transfusions or growth factors within 3 months of treatment start.
• Absolute Neutrophil Count (ANC) ≥1,500/microliter (mcL).
• Creatinine clearance Glomerular filtration rate (GFR) ≥ 60 mL/min/1.73 m\^2 , calculated using the Cockcroft-Gault equation.
• Albumin ≥2.5 g/dL.
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤3.0 x ULN.
• Total bilirubin (TBIL) ≤2 x the institutional upper limit of normal (ULN). For participants with known Gilbert's Syndrome ≤3 x ULN is permitted.
• Ability to understand and the willingness to sign a written informed consent document.
• Participants must provide consent to comply to recommended radioprotection precautions during study.
• Participants must use adequate contraception and not donate sperm while on study drug and for at least 14 weeks after the last study treatment.