This is a phase I clinical trial conducted in participants with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC). After confirmation of PSMA positivity, participants receive intravenous administration of 177Lu-PSMA-VG01. The objectives are: to evaluate the biodistribution, radiation dosimetry, safety and tolerability of 177Lu-PSMA-VG01 in participants; and to assess the pharmacokinetics (PK), preliminary anti-tumor activity, and in vivo stability of 177Lu-PSMA-VG01 in participants.

This is a prospective, single-arm, dose-escalation and open phase I clinical study. 10-24 participants are expected to be enrolled. Participants will sign the informed consent form (ICF) prior to screening.

Only PSMA-positive participants with metastatic castration-resistant prostate cancer (mCRPC) who meet the inclusion criteria and do not meet any exclusion criteria will be enrolled. The successful screened participants will be treated with 177Lu-PSMA-VG01 injection intravenously during the treatment period. Pharmacokinetic (PK) blood samples will be collected, and SPECT/CT imaging will be performed during the clinical study.

Long-term follow-up will last up to 2 years after completion of EOT. Throughout the study period, participants will undergo safety monitoring following drug administration.

Inclusion Criteria:

1. Male participants aged 18 years (inclusive) to 80 years (exclusive) at the time of signing the informed consent.
2. Histologically or cytologically confirmed prostate cancer with no standard treatment options available, or failure/intolerance to standard therapies, or inability to access standard treatment.
3. During the screening period, imaging examinations (within 4 weeks before administration) showed the presence of ≥1 metastatic lesion.
4. ECOG Performance Status score: 0 to 2.
5. Expected survival time exceeds 6 months.
6. All clinically significant toxicities related to prior anti-tumor therapy (e.g., chemotherapy, radiotherapy, etc., excluding Luteinizing Hormone-Releasing Hormone (LHRH) analog therapy) must have resolved to ≤ Grade 1, except for toxicities deemed safe and manageable by the investigator, such as alopecia, peripheral neuropathy ≤ Grade 2, etc. (CTCAE V6.0).
7. The participant must be fully informed about the study and voluntarily provide written informed consent prior to participation.
8. The participant must be capable of understanding and complying with the requirements of the trial protocol.
9. The participant must use a condom during sexual activity throughout the study period and for 14 weeks after the last dose of study treatment to prevent pregnancy in partners and potential exposure of partners to the investigational product g via semen. Additionally, the participant should refrain from sperm donation during the specified timeframe above.

Exclusion Criteria:

1. Having received anti-tumor therapies such as chemotherapy, biological therapy, targeted therapy, or immunotherapy within 4 weeks prior to the first dose of the investigational product, or planning to receive such therapies during the study period.
2. Having received systemic or local radionuclide therapy within 3 months prior to the first dose.
3. Having received other investigational product treatments not yet approved within 4 weeks prior to the first dose of the investigational product, or within five half-lives of that.
4. Having undergone major organ surgery (excluding needle biopsy) or experienced significant trauma within 4 weeks prior to the first dose of the investigational product, or requiring elective surgery during the trial period.
5. Having been diagnosed with other malignancies within the past 2 years (participants with a prior history of malignancy who have received adequate treatment and have remained disease- and treatment-free for over 3 years prior to enrollment are eligible, as are patients with adequately treated non-melanoma skin cancer or superficial bladder cancer).
6. Having symptomatic spinal cord compression or clinical/imaging findings suggestive of impending spinal cord compression.
7. Known allergy to structural analogs of this product or other excipients.
8. Having a history of immunodeficiency, including a positive HIV test result, other acquired or congenital immunodeficiency diseases, or a history of organ transplantation; a history of severe autoimmune diseases deemed unsuitable for enrollment by the investigator; or requiring immunosuppressive therapy for allogeneic organ transplantation.
9. Having severe infections (requiring intravenous antibiotics, antifungals, or antivirals according to clinical practice guidelines), active hepatitis A, active hepatitis B (HBV DNA ≥2000 IU/mL or 10^4 copies/mL; prophylactic antiviral therapy other than interferon is allowed), active hepatitis C (anti-HCV positive and HCV-RNA above the lower limit of detection), or active syphilis infection.
10. Having uncontrolled third-space fluid accumulations (such as significant pleural effusion, ascites or pericardial effusion) deemed unsuitable for enrollment by the investigator.
11. Having a clear history of neurological or psychiatric disorders, including epilepsy or dementia.
12. Other reasons considered by the investigator to make the participant unsuitable for participation in this clinical study.