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

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, Jr, Daniel J.; Mach, Robert H.; Pryma, Daniel A.; Maris, John M.

doi:10.1038/s42003-022-04209-8

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

Journal Article · Thu Nov 17 00:00:00 EST 2022 · Communications Biology

DOI:https://doi.org/10.1038/s42003-022-04209-8· OSTI ID:1898670

Makvandi, Mehran; Samanta, Minu; Martorano, Paul; Lee, Hwan; Gitto, Sarah B.; Patel, Khushbu; ; ; Martinez, Daniel; Riad, Aladdin; Dabagian, Hannah; ; Taghvaee, Tara; Xu, Kuiying; Lee, Ji Youn; ; Farrel, Alvin; Batra, Vandana; Carlin, Sean D.; more »

Abstract

Astatine-211-parthanatine ([ ²¹¹ At]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 [ ²¹¹ At]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 [ ²¹¹ At]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 [ ²¹¹ At]PTT for high-risk neuroblastoma.

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Research Organization:: Univ. of Pennsylvania, Philadelphia, PA (United States)

Sponsoring Organization:: USDOE; USDOE Office of Science (SC), Nuclear Physics (NP)

Grant/Contract Number:: SC0021066

OSTI ID:: 1898670

Alternate ID(s):: OSTI ID: 2421712

Journal Information:: Communications Biology, Journal Name: Communications Biology Journal Issue: 1 Vol. 5; ISSN 2399-3642

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United Kingdom

Language:: English

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