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- Title
Pre-clinical investigation of astatine-211-parthanatine for high-risk neuroblastoma.
- Authors
Makvandi, Mehran; Samanta, Minu; Martorano, Paul; Lee, Hwan; Gitto, Sarah B.; Patel, Khushbu; Groff, David; Pogoriler, Jennifer; Martinez, Daniel; Riad, Aladdin; Dabagian, Hannah; Zaleski, Michael; Taghvaee, Tara; Xu, Kuiying; Lee, Ji Youn; Hou, Catherine; Farrel, Alvin; Batra, Vandana; Carlin, Sean D.; Powell, Daniel J. Jr
- 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 72 days with 30% (6/20) of mice showing no measurable tumor >95 days. Reversible hematological and marrow toxicity was observed 72 hours post-treatment at the MTD, however full recovery was evident by 4 weeks post-therapy. These data support clinical development of [211At]PTT for high-risk neuroblastoma.The efficacy and toxicity of the PARP inhibitor parthanatine, radiolabeled with the alpha particle emitter astatine-211, in 11 patient derived neuroblastoma murine xenografts is investigated.
- Publication
Communications Biology, 2022, Vol 5, Issue 1, p1
- ISSN
2399-3642
- Publication type
Article
- DOI
10.1038/s42003-022-04209-8