Inclusion Criteria:
1. Age ≥ 20 years, ability to understand and willingness to sign informed consent, cooperate with all study-related procedures and assessments including blood tests and imaging
2. Histologically confirmed adenocarcinoma of the prostate with evidence of metastatic castration-resistant prostate cancer (mCRPC)
3. Prior surgical orchiectomy or chemical castration maintained on luteinizing hormone-releasing hormone analog, with a serum testosterone level \<50 ng/dL (castrate range)
4. Prior treated with at least one line of taxane-based chemotherapy unless medically unsuitable, and at least one line of androgen receptor pathway inhibitor (e.g., abiraterone, enzalutamide, apalutamide, or darolutamide)
5. Prior treated with 177Lu-labeled PSMA RLT unless medically unsuitable or declined by the patient
6. Progressive disease defined according to Prostate Cancer Clinical Trials Working Group 3: Either a PSA progression of more than 2 rising PSA values from baseline with intervals ≥ 1 week, or a soft-tissue progression on images per RECIST 1.1 criteria, or a bone progression on images with more than 2 new lesions
7. Evidence of significant PSMA-avid lesions on 68Ga- or 18F-labeled PSMA PET/CT within 12 weeks prior to screening, which defined as 68Ga-PSMA or 18F-PSMA uptake greater than that of liver or spleen parenchyma (depend on the tracer used) in at least one metastatic lesion of any size in any organ system
8. A life expectancy of ≥ 6 months and Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
9. Adequate bone marrow and organ functions 9.1 Hemoglobin ≥ 10 g/dL without RBC transfusion within 4 weeks 9.2 Absolute neutrophil count ≥ 1.5 × 109/L 9.3 Platelet count ≥ 150 × 109/L 9.4 Creatinine clearance ≥ 50 mL/min (Cockcroft-Gault) 9.5 AST and ALT ≤ 3 × ULN, total bilirubin ≤ 1.5 × ULN
10. Willingness to comply with the use of medically acceptable forms of barrier contraception if sexually active
Exclusion Criteria:
1. History of allergic reaction to PSMA-targeted compounds or radiometals
2. Prior radioligand therapy with 223Ra or 177Lu-PSMA within 6 months
3. Prior surgery or radiotherapy within 4 weeks prior to first investigational dose
4. Prior systemic therapies against prostate cancer within 4 weeks, including androgen receptor pathway inhibitor, chemotherapy, targeted therapy such as PARP inhibitors (PARPi)
5. Discordant disease on PET images: FDG-positive disease with minimal PSMA expression
6. Urinary tract obstruction causing hydronephrosis unless appropriately treated beforehand
7. Known symptomatic brain metastases or leptomeningeal disease, symptomatic or impending cord compression unless appropriately treated beforehand
8. Other active malignancy requiring systemic treatment
9. Significant cardiovascular disease (e.g., recent myocardial infarction, unstable angina)
10. Concurrent severe uncontrolled illness that may jeopardize patient safety, including uncontrolled infections
