Targeted alpha anticancer therapies: update and future prospects

Barry J Allen,1,2 Chen-Yu Huang,3 Raymond A Clarke2 1Faculty of Physics, University of Sydney, Sydney, NSW, Australia; 2Faculty of Medicine, Ingham Institute, University of Western Sydney, Liverpool, NSW, Australia; 3Central Clinical School, University of Sydney, Sydney, NSW, AustraliaAbstract: Tar...

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Autores principales:	Allen BJ, Huang CY, Clarke RA
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2014
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/2e454f40cb7b41de9c24a7b890990185
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spelling	oai:doaj.org-article:2e454f40cb7b41de9c24a7b8909901852021-12-02T00:35:09ZTargeted alpha anticancer therapies: update and future prospects1177-5491https://doaj.org/article/2e454f40cb7b41de9c24a7b8909901852014-11-01T00:00:00Zhttp://www.dovepress.com/targeted-alpha-anticancer-therapies-update-and-future-prospects-peer-reviewed-article-BTThttps://doaj.org/toc/1177-5491 Barry J Allen,1,2 Chen-Yu Huang,3 Raymond A Clarke2 1Faculty of Physics, University of Sydney, Sydney, NSW, Australia; 2Faculty of Medicine, Ingham Institute, University of Western Sydney, Liverpool, NSW, Australia; 3Central Clinical School, University of Sydney, Sydney, NSW, AustraliaAbstract: Targeted alpha therapy (TAT) is an emerging option for local and systemic cancer treatment. Preclinical research and clinical trials show that alpha-emitting radionuclides can kill targeted cancer cells while sparing normal cells, thus reducing toxicity. 223RaCl2 (Xofigo®) is the first alpha emitting radioisotope to gain registration in the US for palliative therapy of prostate cancer bone metastases by indirect physiological targeting. The alpha emitting radioisotopes 211At, 213Bi, 225Ac and 227Th are being used to label targeting vectors such as monoclonal antibodies for specific cancer therapy indications. In this review, safety and tolerance aspects are considered with respect to microdosimetry, specific energy, Monte Carlo model calculations, biodosimetry, equivalent dose and mutagenesis. The clinical efficacy of TAT for solid tumors may also be enhanced by its capacity for tumor anti-vascular (TAVAT) effects. This review emphasizes key aspects of TAT research with respect to the PAI2-uPAR complex and the monoclonal antibodies bevacizumab, C595 and J591. Clinical trial outcomes are reviewed for neuroendocrine tumors, leukemia, glioma, melanoma, non-Hodgkins lymphoma, and prostate bone metastases. Recommendations and future directions are proposed.Keywords: biodosimetry, microdosimetry, mutagenesis, PAI2, bevacizumab, C595, J591, tumors, cancer, metastasesAllen BJHuang CYClarke RADove Medical PressarticleMedicine (General)R5-920ENBiologics: Targets & Therapy, Vol 2014, Iss default, Pp 255-267 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Allen BJ Huang CY Clarke RA Targeted alpha anticancer therapies: update and future prospects
description	Barry J Allen,1,2 Chen-Yu Huang,3 Raymond A Clarke2 1Faculty of Physics, University of Sydney, Sydney, NSW, Australia; 2Faculty of Medicine, Ingham Institute, University of Western Sydney, Liverpool, NSW, Australia; 3Central Clinical School, University of Sydney, Sydney, NSW, AustraliaAbstract: Targeted alpha therapy (TAT) is an emerging option for local and systemic cancer treatment. Preclinical research and clinical trials show that alpha-emitting radionuclides can kill targeted cancer cells while sparing normal cells, thus reducing toxicity. 223RaCl2 (Xofigo®) is the first alpha emitting radioisotope to gain registration in the US for palliative therapy of prostate cancer bone metastases by indirect physiological targeting. The alpha emitting radioisotopes 211At, 213Bi, 225Ac and 227Th are being used to label targeting vectors such as monoclonal antibodies for specific cancer therapy indications. In this review, safety and tolerance aspects are considered with respect to microdosimetry, specific energy, Monte Carlo model calculations, biodosimetry, equivalent dose and mutagenesis. The clinical efficacy of TAT for solid tumors may also be enhanced by its capacity for tumor anti-vascular (TAVAT) effects. This review emphasizes key aspects of TAT research with respect to the PAI2-uPAR complex and the monoclonal antibodies bevacizumab, C595 and J591. Clinical trial outcomes are reviewed for neuroendocrine tumors, leukemia, glioma, melanoma, non-Hodgkins lymphoma, and prostate bone metastases. Recommendations and future directions are proposed.Keywords: biodosimetry, microdosimetry, mutagenesis, PAI2, bevacizumab, C595, J591, tumors, cancer, metastases
format	article
author	Allen BJ Huang CY Clarke RA
author_facet	Allen BJ Huang CY Clarke RA
author_sort	Allen BJ
title	Targeted alpha anticancer therapies: update and future prospects
title_short	Targeted alpha anticancer therapies: update and future prospects
title_full	Targeted alpha anticancer therapies: update and future prospects
title_fullStr	Targeted alpha anticancer therapies: update and future prospects
title_full_unstemmed	Targeted alpha anticancer therapies: update and future prospects
title_sort	targeted alpha anticancer therapies: update and future prospects
publisher	Dove Medical Press
publishDate	2014
url	https://doaj.org/article/2e454f40cb7b41de9c24a7b890990185
work_keys_str_mv	AT allenbj targetedalphaanticancertherapiesupdateandfutureprospects AT huangcy targetedalphaanticancertherapiesupdateandfutureprospects AT clarkera targetedalphaanticancertherapiesupdateandfutureprospects
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Targeted alpha anticancer therapies: update and future prospects

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