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 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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Nov 17, 2022
- Source ID
- 10.1038/s42003-022-04209-8
Entities
People
- Aladdin Riad
- Alvin Farrel
- Catherine Hou
- Daniel A. Pryma
- Daniel J Powell
- Daniel Martinez
- David Groff
- Hannah Dabagian
- Hwan Lee
- Jennifer Pogoriler
- Ji Youn Lee
- John M. Maris
- Khushbu Patel
- Kuiying Xu
- Mehran Makvandi
- Michael Zaleski
- Minu Samanta
- Paul Martorano
- Robert H. Mach
- Sarah B. Gitto
- Sean D. Carlin
- Tara Taghvaee
- Vandana Batra
Organizations
- National Cancer Institute
- United States Department of Energy
- United States Department of Health and Human Services