Targeted α-therapy using astatine ((211)At)-labeled PSMA1, 5, and 6: a preclinical evaluation as a novel compound

PURPOSE: Targeted α-therapy (TAT) for prostate-specific membrane antigen (PSMA) is a promising treatment for metastatic castration-resistant prostate cancer (CRPC). Astatine is an α-emitter (half-life=7.2 h) that can be produced by a 30-MeV cyclotron. This study evaluated the treatment effect of (21...

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Detalles Bibliográficos
Autores principales: Watabe, Tadashi, Kaneda-Nakashima, Kazuko, Shirakami, Yoshifumi, Kadonaga, Yuichiro, Ooe, Kazuhiro, Wang, Yang, Haba, Hiromitsu, Toyoshima, Atsushi, Cardinale, Jens, Giesel, Frederik L., Tomiyama, Noriyuki, Fukase, Koichi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2022
Materias:
Original Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9852121/
https://www.ncbi.nlm.nih.gov/pubmed/36344651
http://dx.doi.org/10.1007/s00259-022-06016-z
Descripción
Sumario:PURPOSE: Targeted α-therapy (TAT) for prostate-specific membrane antigen (PSMA) is a promising treatment for metastatic castration-resistant prostate cancer (CRPC). Astatine is an α-emitter (half-life=7.2 h) that can be produced by a 30-MeV cyclotron. This study evaluated the treatment effect of (211)At-labeled PSMA compounds in mouse xenograft models. METHODS: Tumor xenograft models were established by subcutaneous transplantation of human prostate cancer cells (LNCaP) in NOD/SCID mouse. [(211)At]PSMA1, [(211)At]PSMA5, or [(211)At]PSMA6 was administered to LNCaP xenograft mice to evaluate biodistribution at 3 and 24 h. The treatment effect was evaluated by administering [(211)At]PSMA1 (0.40 ± 0.07 MBq), [(211)At]PSMA5 (0.39 ± 0.03 MBq), or saline. Histopathological evaluation was performed for the at-risk organs at 3 and 6 weeks after administration. RESULTS: [(211)At]PSMA5 resulted in higher tumor retention compared to [(211)At]PSMA1 and [(211)At]PSMA6 (30.6 ± 17.8, 12.4 ± 4.8, and 19.1 ± 4.5 %ID/g at 3 h versus 40.7 ± 2.6, 8.7 ± 3.5, and 18.1 ± 2.2%ID/g at 24 h, respectively), whereas kidney excretion was superior in [(211)At]PSMA1 compared to [(211)At]PSMA5 and [(211)At]PSMA6. An excellent treatment effect on tumor growth was observed after [(211)At]PSMA5 administration. [(211)At]PSMA1 also showed a substantial treatment effect; however, the tumor size was relatively larger compared to that with [(211)At]PSMA5. In the histopathological evaluation, regenerated tubules were detected in the kidneys at 3 and 6 weeks after the administration of [(211)At]PSMA5. CONCLUSION: TAT using [(211)At]PSMA5 resulted in excellent tumor growth suppression with minimal side effects in the normal organs. [(211)At]PSMA5 should be considered a new possible TAT for metastatic CRPC, and translational prospective trials are warranted. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00259-022-06016-z.

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