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

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...

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Autores principales: 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., Mach, Robert H., Pryma, Daniel A., Maris, John M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9671962/
https://www.ncbi.nlm.nih.gov/pubmed/36396952
http://dx.doi.org/10.1038/s42003-022-04209-8
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author 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.
Mach, Robert H.
Pryma, Daniel A.
Maris, John M.
author_facet 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.
Mach, Robert H.
Pryma, Daniel A.
Maris, John M.
author_sort Makvandi, Mehran
collection PubMed
description 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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spelling pubmed-96719622022-11-19 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, Daniel J. Mach, Robert H. Pryma, Daniel A. Maris, John M. Commun Biol Article 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. Nature Publishing Group UK 2022-11-17 /pmc/articles/PMC9671962/ /pubmed/36396952 http://dx.doi.org/10.1038/s42003-022-04209-8 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
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.
Mach, Robert H.
Pryma, Daniel A.
Maris, John M.
Pre-clinical investigation of astatine-211-parthanatine for high-risk neuroblastoma
title Pre-clinical investigation of astatine-211-parthanatine for high-risk neuroblastoma
title_full Pre-clinical investigation of astatine-211-parthanatine for high-risk neuroblastoma
title_fullStr Pre-clinical investigation of astatine-211-parthanatine for high-risk neuroblastoma
title_full_unstemmed Pre-clinical investigation of astatine-211-parthanatine for high-risk neuroblastoma
title_short Pre-clinical investigation of astatine-211-parthanatine for high-risk neuroblastoma
title_sort pre-clinical investigation of astatine-211-parthanatine for high-risk neuroblastoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9671962/
https://www.ncbi.nlm.nih.gov/pubmed/36396952
http://dx.doi.org/10.1038/s42003-022-04209-8
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