Pre-clinical investigation of astatine-211-parthanatine for high-risk neuroblastoma.

ABSTRACT: Astatine-211-parthanatine ([²¹¹At]PTT) is an alpha-emitting radiopharmaceutical therapeutic that targets poly(adenosine-diphosphate-ribose) polymerase 1 (PARP1) in cancer cells. High-risk neuroblastomas exhibit among the highest PARP1 expression across solid tumors. In this study, we evaluated the efficacy of [²¹¹At]PTT using 11 patient-derived xenograft (PDX) mouse models of high-risk neuroblastoma, and assessed hematological and marrow toxicity in a CB57/BL6 healthy mouse model. We observed broad efficacy in PDX models treated with [²¹¹At]PTT at the maximum tolerated dose (MTD 36 MBq/kg/fraction x4) administered as a fractionated regimen. For the MTD, complete tumor response was observed in 81.8% (18 of 22) of tumors and the median event free survival was

SUBMITTER: Makvandi M 

PROVIDER: S-EPMC9671962 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature