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Targeted alpha anticancer therapies: update and future prospects

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. (223)RaCl(2) (Xofigo(®)) is the first alpha e...

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Autores principales: Allen, Barry J, Huang, Chen-Yu, Clarke, Raymond A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4232037/
https://www.ncbi.nlm.nih.gov/pubmed/25422581
http://dx.doi.org/10.2147/BTT.S29947
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author Allen, Barry J
Huang, Chen-Yu
Clarke, Raymond A
author_facet Allen, Barry J
Huang, Chen-Yu
Clarke, Raymond A
author_sort Allen, Barry J
collection PubMed
description 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. (223)RaCl(2) (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 (211)At, (213)Bi, (225)Ac and (227)Th 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.
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spelling pubmed-42320372014-11-24 Targeted alpha anticancer therapies: update and future prospects Allen, Barry J Huang, Chen-Yu Clarke, Raymond A Biologics Review 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. (223)RaCl(2) (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 (211)At, (213)Bi, (225)Ac and (227)Th 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. Dove Medical Press 2014-11-10 /pmc/articles/PMC4232037/ /pubmed/25422581 http://dx.doi.org/10.2147/BTT.S29947 Text en © 2014 Allen et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Review
Allen, Barry J
Huang, Chen-Yu
Clarke, Raymond A
Targeted alpha anticancer therapies: update and future prospects
title 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_short Targeted alpha anticancer therapies: update and future prospects
title_sort targeted alpha anticancer therapies: update and future prospects
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4232037/
https://www.ncbi.nlm.nih.gov/pubmed/25422581
http://dx.doi.org/10.2147/BTT.S29947
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