Delayed Nephrotoxicity After 225Ac-PSMA-617 Radioligand Therapy

Area of Science:

• Oncology
• Radiopharmaceuticals
• Nuclear Medicine

Background:

• Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) is an emerging treatment for metastatic castration-resistant prostate cancer (mCRPC).
• Alpha-emitter therapies like 225Ac-PSMA-617 offer improved efficacy over beta-emitters (e.g., 177Lu-PSMA-617).
• While early toxicities like xerostomia and myelosuppression are known, long-term adverse events require further investigation.

Observation:

• A 76-year-old male patient with mCRPC received 2 cycles of 225Ac-PSMA-617 RLT.
• The patient experienced an excellent initial response to the therapy.
• Delayed nephrotoxicity, specifically tubulointerstitial nephritis, was observed after treatment.

Findings:

• 225Ac-PSMA-617 RLT can induce delayed kidney toxicity, presenting as tubulointerstitial nephritis.
• This adverse event occurred despite an initial positive response to the therapy.
• The case highlights the need for monitoring long-term organ function in patients undergoing PSMA-RLT.

Implications:

• Further research is needed to understand and mitigate the long-term toxicities of 225Ac-PSMA-617 RLT.
• Clinical monitoring protocols may need to incorporate long-term renal function assessment.
• This case contributes to the understanding of the safety profile of advanced radioligand therapies for prostate cancer.