Evaluation of the therapeutic efficacy of 225Ac-PSMA I&T in advanced prostate cancer: preliminary results

Aim/Introduction: Prostate-specifc membrane antigen (PSMA) is a protein highly expressed on the surface of prostate cancer cells, making it an ideal target for therapy. The use of 225Ac-PSMA-617 to treat advanced prostate cancer has shown remarkable efcacy without signifcant side efects. The treatment relies on accurately delivering the radiopharmaceutical to cancer cells with elevated PSMA receptor expression, leveraging the potent impact of alpha radiation on tumor DNA. Our study aims to assess the efficacy and safety of 225Ac-PSMA I&T in patients with prostate cancer who have shown disease progression despite previous treatment modalities. Materials and Methods: Ten patients diagnosed with metastatic castration-resistant prostate cancer underwent a treatment regimen involving four cycles of 225Ac-PSMA I&T at 100 kBq/kg, administered at two-month intervals. All patients had previously received extensive chemotherapy and hormonal therapy before their enrollment. After each treatment cycle, urine and blood samples were collected at three-time points for upto 24 hours to assess the clearance rate. The prostate-specifc antigen (PSA) levels and blood cell counts were measured throughout the treatment regimen every four weeks. PET/CT using 68Ga PSMA-11 was used for baseline staging and imaging control after treatment. The local research ethics committee approved the study. Results: Preliminary results from this ongoing study demonstrate the auspicious therapeutic efcacy of 225AcPSMA I&T in patients with progressive prostate cancer. The early evaluation shows favourable response rates, including signifcant reductions in PSA concentrations of 26.7% to 36.5% after the frst dose of 225Ac-PSMA I&T and from 77.5% to 93.8% after the second dose compared to baseline. The 68Ga-PSMA-11 PET/CT images prove tumor regression compared to baseline scans. Importantly, the treatment is well-tolerated, with no signifcant treatment-related adverse events reported thus far. Conclusion:Targeted α-therapy with the use of 225Ac-PSMA I&T is very promising and provides the possibility of efective treatment of advanced-stage prostate cancer patients progressing on existing treatment lines. Additional research involving a larger cohort of patients is necessary to evaluate the efcacy and safety of the treatment comprehensively.

BUDLEWSKI Tadeusz;  MAJKOWSKA PILIP Agnieszka;  BRUCHERTSEIFER Frank;  BISLKA-SOBECKA A;  IRTYCH B;  WALCZAK Rafal;  MORGENSTERN Alfred;  WALECKI J; 

2024-12-17

SPRINGER

JRC139971

1619-7089 (online),   

https://link.springer.com/article/10.1007/s00259-024-06838-z,    https://publications.jrc.ec.europa.eu/repository/handle/JRC139971,   

10.1007/s00259-024-06838-z (online),