European journal of nuclear medicine and molecular imaging · 2026
Clinical research analysis of [225Ac]Ac-PSMA-617 therapy for [177Lu]Lu-PSMA-refractory metastatic castration-resistant prostate cancer.
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Rao Zijuan, Ma Jiao, Jiangchu Yangqing, Yang Weiyu, Zhang Fengyu, Hu Meiling, Zhang Chunyin, Chen Yue
Аннотация
OBJECTIVE: The aim of this evaluation was to identify the safety and efficacy for [225Ac]Ac-labeled prostate-specific membrane antigen-617 therapy in a retrospectively analyzed group of patients after [177Lu]Lu-PSMA therapy.
METHODS: Metastatic castration-resistant prostate cancer patients after [177Lu]Lu-PSMA were selected for treatment with 1 ~ 5 cycles of [225Ac]Ac-PSMA-617. Prostate-specific antigen and blood cell count were measured at the 2nd, 4th, and 8th week after treatment. [68Ga]Ga-PSMA-11 PET/CT was used for baseline staging and imaging follow-up at the 2nd month. Safety was assessed according to the Common Terminology Criteria for Adverse Events version 5.0.
RESULTS: Eighteen patients were treated per protocol with a mean activity of 6.1 MBq in each cycle. 72.22% had a PSA decline at any degree, 55.56% had a PSA decline at more than 50%, and 38.89% had a PSA decline at more than 80%. According to PSMA PET progression criteria, disease control was achieved in 38.89% of the patients. The median progression-free survival under [225Ac]Ac-PSMA-617 after [177Lu]Lu-PSMA therapy was 4 mo; the median overall survival was 17 mo. Any decline in PSA, a decline in PSA of ≥ 50%, prior treatment with at least 2 cycles and at least 3 cycles of [177Lu]Lu-PSMA were all significantly associated with PFS. The median PFS was significantly longer for patients receiving ≥ 2 cycles of [177Lu]Lu-PSMA therapy (4.8 mo, 95% CI: 3.7-5.9) compared to those receiving only 1 cycle (2.4 mo, 95% CI: 1.6-3.2). Median PFS was 5.3 mo (95% CI: 4.0-6.5) with ≥ 3 cycles of [177Lu]Lu-PSMA therapy, compared to 3 mo (95% CI: 2.0-4.0) in those receiving < 3 cycles.Toxic reactions and adverse effects were mostly grade I ~ III and anemia is the most common hematological toxic reaction. The change in hemoglobin levels before and after [225Ac]Ac-PSMA treatment was statistically significant (p = 0.006). All patients experienced xerostomia to varying degrees.
CONCLUSION: For metastatic castration-resistant prostate cancer patients intolerant or unresponsive to [177Lu]Lu-PSMA treatment, [225Ac]Ac-PSMA-617 demonstrated significant and safe antitumor effects with relatively low treatment-related toxicity.
METHODS: Metastatic castration-resistant prostate cancer patients after [177Lu]Lu-PSMA were selected for treatment with 1 ~ 5 cycles of [225Ac]Ac-PSMA-617. Prostate-specific antigen and blood cell count were measured at the 2nd, 4th, and 8th week after treatment. [68Ga]Ga-PSMA-11 PET/CT was used for baseline staging and imaging follow-up at the 2nd month. Safety was assessed according to the Common Terminology Criteria for Adverse Events version 5.0.
RESULTS: Eighteen patients were treated per protocol with a mean activity of 6.1 MBq in each cycle. 72.22% had a PSA decline at any degree, 55.56% had a PSA decline at more than 50%, and 38.89% had a PSA decline at more than 80%. According to PSMA PET progression criteria, disease control was achieved in 38.89% of the patients. The median progression-free survival under [225Ac]Ac-PSMA-617 after [177Lu]Lu-PSMA therapy was 4 mo; the median overall survival was 17 mo. Any decline in PSA, a decline in PSA of ≥ 50%, prior treatment with at least 2 cycles and at least 3 cycles of [177Lu]Lu-PSMA were all significantly associated with PFS. The median PFS was significantly longer for patients receiving ≥ 2 cycles of [177Lu]Lu-PSMA therapy (4.8 mo, 95% CI: 3.7-5.9) compared to those receiving only 1 cycle (2.4 mo, 95% CI: 1.6-3.2). Median PFS was 5.3 mo (95% CI: 4.0-6.5) with ≥ 3 cycles of [177Lu]Lu-PSMA therapy, compared to 3 mo (95% CI: 2.0-4.0) in those receiving < 3 cycles.Toxic reactions and adverse effects were mostly grade I ~ III and anemia is the most common hematological toxic reaction. The change in hemoglobin levels before and after [225Ac]Ac-PSMA treatment was statistically significant (p = 0.006). All patients experienced xerostomia to varying degrees.
CONCLUSION: For metastatic castration-resistant prostate cancer patients intolerant or unresponsive to [177Lu]Lu-PSMA treatment, [225Ac]Ac-PSMA-617 demonstrated significant and safe antitumor effects with relatively low treatment-related toxicity.
Предметные рубрики MeSH
HumansMaleProstatic Neoplasms, Castration-ResistantHeterocyclic Compounds, 1-RingDipeptidesLutetiumAgedNeoplasm MetastasisMiddle AgedPositron Emission Tomography Computed TomographyRetrospective StudiesProstate-Specific AntigenActiniumRadioisotopesTreatment OutcomeRadiopharmaceuticalsAged, 80 and over