Targeted radionuclide therapy with astatine-211: Oxidative dehalogenation of astatobenzoate conjugates

Abstract 211At is a most promising radionuclide for targeted alpha therapy. However, its limited availability and poorly known basic chemistry hamper its use. Based on the analogy with iodine, labelling is performed via astatobenzoate conjugates, but in vivo deastatination occurs, particularly when...

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Autores principales:	David Teze, Dumitru-Claudiu Sergentu, Valentina Kalichuk, Jacques Barbet, David Deniaud, Nicolas Galland, Rémi Maurice, Gilles Montavon
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ed78f40f24454144bfa69cd69a69a850
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spelling	oai:doaj.org-article:ed78f40f24454144bfa69cd69a69a8502021-12-02T16:07:50ZTargeted radionuclide therapy with astatine-211: Oxidative dehalogenation of astatobenzoate conjugates10.1038/s41598-017-02614-22045-2322https://doaj.org/article/ed78f40f24454144bfa69cd69a69a8502017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02614-2https://doaj.org/toc/2045-2322Abstract 211At is a most promising radionuclide for targeted alpha therapy. However, its limited availability and poorly known basic chemistry hamper its use. Based on the analogy with iodine, labelling is performed via astatobenzoate conjugates, but in vivo deastatination occurs, particularly when the conjugates are internalized in cells. Actually, the chemical or biological mechanism responsible for deastatination is unknown. In this work, we show that the C−At “organometalloid” bond can be cleaved by oxidative dehalogenation induced by oxidants such as permanganates, peroxides or hydroxyl radicals. Quantum mechanical calculations demonstrate that astatobenzoates are more sensitive to oxidation than iodobenzoates, and the oxidative deastatination rate is estimated to be about 6 × 106 faster at 37 °C than the oxidative deiodination one. Therefore, we attribute the “internal” deastatination mechanism to oxidative dehalogenation in biological compartments, in particular lysosomes.David TezeDumitru-Claudiu SergentuValentina KalichukJacques BarbetDavid DeniaudNicolas GallandRémi MauriceGilles MontavonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q David Teze Dumitru-Claudiu Sergentu Valentina Kalichuk Jacques Barbet David Deniaud Nicolas Galland Rémi Maurice Gilles Montavon Targeted radionuclide therapy with astatine-211: Oxidative dehalogenation of astatobenzoate conjugates
description	Abstract 211At is a most promising radionuclide for targeted alpha therapy. However, its limited availability and poorly known basic chemistry hamper its use. Based on the analogy with iodine, labelling is performed via astatobenzoate conjugates, but in vivo deastatination occurs, particularly when the conjugates are internalized in cells. Actually, the chemical or biological mechanism responsible for deastatination is unknown. In this work, we show that the C−At “organometalloid” bond can be cleaved by oxidative dehalogenation induced by oxidants such as permanganates, peroxides or hydroxyl radicals. Quantum mechanical calculations demonstrate that astatobenzoates are more sensitive to oxidation than iodobenzoates, and the oxidative deastatination rate is estimated to be about 6 × 106 faster at 37 °C than the oxidative deiodination one. Therefore, we attribute the “internal” deastatination mechanism to oxidative dehalogenation in biological compartments, in particular lysosomes.
format	article
author	David Teze Dumitru-Claudiu Sergentu Valentina Kalichuk Jacques Barbet David Deniaud Nicolas Galland Rémi Maurice Gilles Montavon
author_facet	David Teze Dumitru-Claudiu Sergentu Valentina Kalichuk Jacques Barbet David Deniaud Nicolas Galland Rémi Maurice Gilles Montavon
author_sort	David Teze
title	Targeted radionuclide therapy with astatine-211: Oxidative dehalogenation of astatobenzoate conjugates
title_short	Targeted radionuclide therapy with astatine-211: Oxidative dehalogenation of astatobenzoate conjugates
title_full	Targeted radionuclide therapy with astatine-211: Oxidative dehalogenation of astatobenzoate conjugates
title_fullStr	Targeted radionuclide therapy with astatine-211: Oxidative dehalogenation of astatobenzoate conjugates
title_full_unstemmed	Targeted radionuclide therapy with astatine-211: Oxidative dehalogenation of astatobenzoate conjugates
title_sort	targeted radionuclide therapy with astatine-211: oxidative dehalogenation of astatobenzoate conjugates
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/ed78f40f24454144bfa69cd69a69a850
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Targeted radionuclide therapy with astatine-211: Oxidative dehalogenation of astatobenzoate conjugates

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