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Cancer radioimmunotherapy with alpha-emitting nuclides

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Abstract

In lymphoid malignancies and in certain solid cancers such as medullary thyroid carcinoma, somewhat mixed success has been achieved when applying radioimmunotherapy (RIT) with β-emitters for the treatment of refractory cases. The development of novel RIT with α-emitters has created new opportunities and theoretical advantages due to the high linear energy transfer (LET) and the short path length in biological tissue of α-particles. These physical properties offer the prospect of achieving selective tumoural cell killing. Thus, RIT with α-emitters appears particularly suited for the elimination of circulating single cells or cell clusters or for the treatment of micrometastases at an early stage. However, to avoid non-specific irradiation of healthy tissues, it is necessary to identify accessible tumoural targets easily and rapidly. For this purpose, a small number of α-emitters have been investigated, among which only a few have been used for in vivo preclinical studies. Another problem is the availability and cost of these radionuclides; for instance, the low cost and the development of a reliable actinium-225/bismuth-213 generator were probably determining elements in the choice of bismuth-213 in the only human trial of RIT with an α-emitter. This article reviews the literature concerning monoclonal antibodies radiolabelled with α-emitters that have been developed for possible RIT in cancer patients. The principal radio-immunoconjugates are considered, starting with physical and chemical properties of α-emitters, their mode of production, the possibilities and difficulties of labelling, in vitro studies and finally, when available, in vivo preclinical and clinical studies.

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  1. INSERM U 601, quai Moncousu, Nantes, 44035, France

    Olivier Couturier, Stéphane Supiot, Marie Degraef-Mougin, Alain Faivre-Chauvet, Thomas Carlier, Jean-François Chatal, François Davodeau & Michel Cherel

  2. Department of Nuclear Medicine, Place Alexis Ricordeau, Hôtel Dieu, 44093, Nantes, Cedex, France

    Olivier Couturier

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  1. Olivier Couturier
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Couturier, O., Supiot, S., Degraef-Mougin, M. et al. Cancer radioimmunotherapy with alpha-emitting nuclides. Eur J Nucl Med Mol Imaging 32, 601–614 (2005). https://doi.org/10.1007/s00259-005-1803-2

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