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

• DOI: 10.1007/s00259-022-06016-z
• Publication Date: 2022-11-08T04:30:44Z
• Authors: Tadashi Watabe; Kazuko Kaneda-Nak...; Yoshifumi Shirakami; Yuichiro Kadonaga; Kazuhiro Ooe; Yang Wang; Hiromitsu Haba; Atsushi Toyoshima; Jens Cardinale; Frederik L. Giesel; Noriyuki Tomiyama; Koichi Fukase
• Keywords: Biodistribution

Targeted α-therapy (TAT) for prostate-specific membrane antigen (PSMA) is a promising treatment metastatic castration-resistant prostate cancer (CRPC). Astatine an α-emitter (half-life=7.2 h) that can be produced by 30-MeV cyclotron. This study evaluated the effect of 211At-labeled PSMA compounds in mouse xenograft models.Tumor models were established subcutaneous transplantation human cells (LNCaP) NOD/SCID mouse. [211At]PSMA1, [211At]PSMA5, or [211At]PSMA6 was administered to LNCaP mice evaluate biodistribution at 3 and 24 h. The administering [211At]PSMA1 (0.40 ± 0.07 MBq), [211At]PSMA5 (0.39 0.03 saline. Histopathological evaluation performed at-risk organs 6 weeks after administration.[211At]PSMA5 resulted higher tumor retention compared (30.6 17.8, 12.4 4.8, 19.1 4.5 %ID/g h versus 40.7 2.6, 8.7 3.5, 18.1 2.2%ID/g h, respectively), whereas kidney excretion superior [211At]PSMA6. An excellent on growth observed administration. also showed substantial effect; however, size relatively larger with [211At]PSMA5. In histopathological evaluation, regenerated tubules detected kidneys administration [211At]PSMA5.TAT using suppression minimal side effects normal organs. should considered new possible TAT CRPC, translational prospective trials are warranted.