Enhanced Antitumor Efficacy of Ac-NM600 Compared to Lu-NM600 in Prostate Cancer Models.
1/5 보강
[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%.
- 표본수 (n) 9
APA
Ferreira CA, Potluri HK, et al. (2025). Enhanced Antitumor Efficacy of Ac-NM600 Compared to Lu-NM600 in Prostate Cancer Models.. International journal of radiation oncology, biology, physics. https://doi.org/10.1016/j.ijrobp.2025.09.072
MLA
Ferreira CA, et al.. "Enhanced Antitumor Efficacy of Ac-NM600 Compared to Lu-NM600 in Prostate Cancer Models.." International journal of radiation oncology, biology, physics, 2025.
PMID
41319721 ↗
Abstract 한글 요약
[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 (Ac) versus β (Lu) radiopharmaceutical therapy using NM600 in murine PCa models.
[METHODS AND MATERIALS] NM600 was radiolabeled with Lu and Ac 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 Lu-NM600 in the tail vein. We calculated the dosimetry of Lu-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 Lu-NM600, and 7.4 (low IA) or 18.5 KBq (high IA) of Ac-NM600. Finally, the overall survival and tumor growth rate were monitored periodically for all groups.
[RESULTS] Both Ac/Lu-NM600 demonstrated tumor-specific uptake and retention. Ac-NM600 exhibited superior antitumor effects and significantly improved overall survival compared to Lu-NM600 at similar doses. The enhanced efficacy of Ac-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] Ac-NM600 demonstrated enhanced antitumor efficacy compared to Lu-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 Lu and Ac 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 Lu-NM600 in the tail vein. We calculated the dosimetry of Lu-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 Lu-NM600, and 7.4 (low IA) or 18.5 KBq (high IA) of Ac-NM600. Finally, the overall survival and tumor growth rate were monitored periodically for all groups.
[RESULTS] Both Ac/Lu-NM600 demonstrated tumor-specific uptake and retention. Ac-NM600 exhibited superior antitumor effects and significantly improved overall survival compared to Lu-NM600 at similar doses. The enhanced efficacy of Ac-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] Ac-NM600 demonstrated enhanced antitumor efficacy compared to Lu-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.