Method of screening groups of radioactive molecules and...

G - Physics – 01 – N

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G01N 33/50 (2006.01) C07K 5/10 (2006.01)

Patent

CA 2486911

The invention relates to an amplification-free method of screening groups of radioactive molecules, the products from the molecule groups obtained and the application thereof in order to identify molecules that are capable of binding selectively to a tissue or a particular organ. The inventive method can be used for the development of novel therapeutic compounds and contrast agents for medical imaging and for the screening of medicaments. Said method of screening a group of molecules is characterised in that it comprises at least the following steps: (1) the group of molecules is administered to at least one animal, each molecule being marked first by a suitable radioactive isotope; (2) at least one of the animals is slaughtered and the tissue distribution of the radioactivity of the molecules administered is analysed from sections of tissue or organs taken using suitable imaging devices; (3) sections of tissue or organs in which a radioactivity signal is detected are selected; (4) radioactive fractions from the aforementioned sections of tissue or organs selected during step 3 are isolated using suitable techniques such as chromatography and/or extraction techniques; and (5) the molecule(s) from the radioactive fractions obtained in step 4 are characterised using suitable analysis techniques such as chromatography and/or mass spectrometry. According to one variation of the method, in step 2, where possible, the tissue distribution of the radioactivity of the molecules administered is analysed in vivo using suitable imaging devices from a biological sample which is pre-extracted and selected from the group containing cells and sections of tissue or organs. As a result, said variation does not require the animal to be slaughtered.

Procédé de criblage, sans amplification, de banques de molécules radioactives, produits des banques de molécules obtenues ainsi qu'application du procédé à l'identification de molécules capables de se fixer sélectivement à un tissu ou à un organe particulier, utiles au développement de nouveaux composés thérapeutiques, d'agents de contraste pour l'imagerie médicale et au ciblage de médicaments. Le procédé de criblage d'une banque de molécules est caractérisé en ce qu'il comprend au moins les étapes suivantes: (1) l'administration, à au moins un animal, de ladite banque de molécules, dont chaque molécule est préalablement marquée, par un isotope radioactif convenable, (2) le sacrifice d'au moins l'un des animaux et l'analyse de la distribution tissulaire de la radioactivité des molécules administrées, à partir de coupes de tissus ou d'organes prélevés, à l'aide d'imageurs convenables, (3) la sélection de coupes de tissus ou d'organes dans le(s)quel(s) un signal de radioactivité est détecté, (4) l'isolement, à partir desdites coupes de tissus ou d'organes, sélectionnées à l'étape (3) de fractions radioactives, par des techniques convenables, telles que des techniques d'extraction et/ou de chromatographie et (5) la caractérisation à partir des fractions radioactives obtenues à l'étape (4) de ladite ou desdites molécules, par des techniques d'analyse convenables, telles que la chromatographe et/ou la spectrométrie de masse. En variante, quand cela est possible, l'étape (2) comprend l'analyse de la distribution tissulaire de la radioactivité des molécules administrées, à l'aide d'imageurs convenables, in vitro, à partir d'un échantillon biologique préalablement extrait et sélectionné dans le groupe constitué par des cellules et des coupes de tissus ou d'organes. Cette variante ne nécessite donc pas le sacrifice de l'animal.

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