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

Autor: Makvandi M; Division of Nuclear Medicine and Clinical Molecular Imaging, Department of Radiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA., Samanta M; Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Colket Translational Research Building, 3501 Civic Center Boulevard, Philadelphia, PA, 19104, USA., Martorano P; Division of Nuclear Medicine and Clinical Molecular Imaging, Department of Radiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA., Lee H; Division of Nuclear Medicine and Clinical Molecular Imaging, Department of Radiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA., Gitto SB; Ovarian Cancer Research Center, Division of Gynecology Oncology, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.; Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, 19104, USA.; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA., Patel K; Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Colket Translational Research Building, 3501 Civic Center Boulevard, Philadelphia, PA, 19104, USA., Groff D; Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Colket Translational Research Building, 3501 Civic Center Boulevard, Philadelphia, PA, 19104, USA., Pogoriler J; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA., Martinez D; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA., Riad A; Division of Nuclear Medicine and Clinical Molecular Imaging, Department of Radiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA., Dabagian H; Division of Nuclear Medicine and Clinical Molecular Imaging, Department of Radiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA., Zaleski M; Division of Nuclear Medicine and Clinical Molecular Imaging, Department of Radiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA., Taghvaee T; Division of Nuclear Medicine and Clinical Molecular Imaging, Department of Radiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA., Xu K; Division of Nuclear Medicine and Clinical Molecular Imaging, Department of Radiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA., Lee JY; Division of Nuclear Medicine and Clinical Molecular Imaging, Department of Radiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA., Hou C; Division of Nuclear Medicine and Clinical Molecular Imaging, Department of Radiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA., Farrel A; Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Colket Translational Research Building, 3501 Civic Center Boulevard, Philadelphia, PA, 19104, USA., Batra V; Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Colket Translational Research Building, 3501 Civic Center Boulevard, Philadelphia, PA, 19104, USA., Carlin SD; Division of Nuclear Medicine and Clinical Molecular Imaging, Department of Radiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA., Powell DJ Jr; Ovarian Cancer Research Center, Division of Gynecology Oncology, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.; Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, 19104, USA.; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA., Mach RH; Division of Nuclear Medicine and Clinical Molecular Imaging, Department of Radiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA., Pryma DA; Division of Nuclear Medicine and Clinical Molecular Imaging, Department of Radiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA. daniel.pryma@uphs.upenn.edu., Maris JM; Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Colket Translational Research Building, 3501 Civic Center Boulevard, Philadelphia, PA, 19104, USA. Maris@chop.edu.; Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, USA. Maris@chop.edu.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2022 Nov 17; Vol. 5 (1), pp. 1260. Date of Electronic Publication: 2022 Nov 17.
DOI: 10.1038/s42003-022-04209-8
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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