International journal of radiation oncology, biology, physics · 2025
Enhanced Antitumor Efficacy of 225Ac-NM600 Compared to 177Lu-NM600 in Prostate Cancer Models.
СтатьяСравнительное исследованиеПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
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Ferreira Carolina A, Potluri Hemanth K, Tantawy Ahmed A, Massey Christopher F, Grudzinski Joseph J, Carston Amanda M, Clemons Nathan B, Idrissou Malick Bio, Thickens Anna S, Rosenkrans Zachary T, Choi Cynthia, Kerr Caroline P, Pinchuk Anatoly N, Kwon Ohyun, Jeffery Justin J, Bednarz Bryan P, Morris Zachary S, Weichert Jamey P, McNeel Douglas G, Hernandez Reinier
Аннотация
PURPOSE: Many men with prostate cancer (PCa) develop metastatic castration-resistant PCa (mCRPC) after current treatment, which has a death rate of more than 50%. Although many approaches target mCRPC and show promising results, mCRPC is still incurable. Therefore, we aimed to investigate the efficacy and dosimetry of α (225Ac) versus β (177Lu) radiopharmaceutical therapy using NM600 in murine PCa models.
METHODS AND MATERIALS: NM600 was radiolabeled with 177Lu and 225Ac for radiopharmaceutical therapy studies in immunocompetent mice. Single-photon emission computed tomography (SPECT)/CT imaging was conducted on syngeneic Myc-CaP and TRAMP-C1 PCa mouse models administered 7.4 MBq of 177Lu-NM600 in the tail vein. We calculated the dosimetry of 177Lu-NM600 therapy using SPECT/CT imaging and biodistribution data. Complete blood count, comprehensive metabolic panel, and histology analysis were carried out to assess toxicity in Myc-CaP and TRAMP-C1-beering mice (n = 9), which were given 5.55 (low injected activity [IA]) or 18.5 MBq (high IA) of 177Lu-NM600, and 7.4 (low IA) or 18.5 KBq (high IA) of 225Ac-NM600. Finally, the overall survival and tumor growth rate were monitored periodically for all groups.
RESULTS: Both 225Ac/177Lu-NM600 demonstrated tumor-specific uptake and retention. 225Ac-NM600 exhibited superior antitumor effects and significantly improved overall survival compared to 177Lu-NM600 at similar doses. The enhanced efficacy of 225Ac-NM600 was attributed to its higher relative biological effectiveness. Toxicity studies revealed transient, dose-dependent hematological changes for both agents, with no significant long-term adverse effects.
CONCLUSIONS: 225Ac-NM600 demonstrated enhanced antitumor efficacy compared to 177Lu-NM600 in murine PCa models, with a favorable toxicity profile. These outcomes reveal a strong rationale for further developing α-emitting radiopharmaceutical therapy agents for PCa treatment.
METHODS AND MATERIALS: NM600 was radiolabeled with 177Lu and 225Ac for radiopharmaceutical therapy studies in immunocompetent mice. Single-photon emission computed tomography (SPECT)/CT imaging was conducted on syngeneic Myc-CaP and TRAMP-C1 PCa mouse models administered 7.4 MBq of 177Lu-NM600 in the tail vein. We calculated the dosimetry of 177Lu-NM600 therapy using SPECT/CT imaging and biodistribution data. Complete blood count, comprehensive metabolic panel, and histology analysis were carried out to assess toxicity in Myc-CaP and TRAMP-C1-beering mice (n = 9), which were given 5.55 (low injected activity [IA]) or 18.5 MBq (high IA) of 177Lu-NM600, and 7.4 (low IA) or 18.5 KBq (high IA) of 225Ac-NM600. Finally, the overall survival and tumor growth rate were monitored periodically for all groups.
RESULTS: Both 225Ac/177Lu-NM600 demonstrated tumor-specific uptake and retention. 225Ac-NM600 exhibited superior antitumor effects and significantly improved overall survival compared to 177Lu-NM600 at similar doses. The enhanced efficacy of 225Ac-NM600 was attributed to its higher relative biological effectiveness. Toxicity studies revealed transient, dose-dependent hematological changes for both agents, with no significant long-term adverse effects.
CONCLUSIONS: 225Ac-NM600 demonstrated enhanced antitumor efficacy compared to 177Lu-NM600 in murine PCa models, with a favorable toxicity profile. These outcomes reveal a strong rationale for further developing α-emitting radiopharmaceutical therapy agents for PCa treatment.