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Molecular imaging of the infection by Clostridiodes difficile

20th national competition for scientific and technical research

Infection: early warning, prevention and treatment

Senior Researcher : Beatriz Salinas Rodríguez

Research Centre or Institution : Fundación para la Investigación Biomédica del Hospital Gregorio Marañón. Madrid

Abstract

The general objective of the project is the development of a new technology based on selective radioactive antibodies to C. difficile and its in vivo evaluation in animal models as a non-invasive tool capable of determining the degree of severity of infection, as well as the response to treatment and ability to detect relapses by immunoPET imaging.

Results: Although the timeline described in the project report proposed to start with SO1 (Synthesis of new C. difficile selective tracers based on the commercial antibodies Actoxumab and Bezlotoxumab), the company in charge of supplying us with the antibodies did not have stock, which has delayed the development of this objective. Therefore, and in order to continue with the progress of the project, we have started with the biological tests aimed at achieving SO3 (Evaluation of C. difficile infection, aggressiveness and response to treatment by immunoPET). Since the target of study are toxins A and B released by C. difficile, and not all strains produce the same amount of toxins, we have analyzed these toxins in various strains of C. difficile by fluorescent assays.

The study showed that the strains with the highest toxin A production capacity were strains ATCC 43255 (ribotype 087, mouse), 14243227 (ribotype 027, mouse), 21275839 (ribotype unknown) and 22054445 (ribotype unknown), while the strains with the highest toxin B production capacity were ATCC strains 43255 (ribotype 087, mouse), 14243227 (ribotype 027, mouse) and, above all, strain 21275839 (ribotype 027).

These results have been decisive both in developing the animal model and in analyzing the behavior of the radiotracer, since we expect that its diagnostic capacity will be directly proportional to the amount of toxins produced. Based on these results, we have begun to develop the animal model using ribotype 087 and 027 strains, as these are the strains with the highest presence of toxins.

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