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20th National Research Competition in Life and Earth Sciences
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
The overall objective of the project is the development of new imaging agents based on selective radioactive antibodies to C. difficile and their in vivo evaluation in animal models as a non-invasive tool capable of determining the degree of severity of the infection, as well as the response to treatment and the ability to detect relapses by immunoPET imaging. To date, the synthesis and characterization of tracers based on the commercial antibody Bezlotoxumab radioactively labeled with the isotopes Zirconium 89 (89Zr) and Gallium 68 (68Ga) has been successfully carried out. The results obtained in this first work package "PT1.- Synthesis, validation and evaluation of new imaging agents based on anti-C. difficile antibodies" have demonstrated a compound purity >99%, a high radiochemical yield (83.7±1.3%, in the case of 89Zr-Bezlo and 47±10.7%) and a high specific activity (1.6±0.1mCi/mg). Although the project proposed the development of tracers using the commercial antibodies Bezlotoxumab and Actoxumab, the withdrawal of the latter from the market due to negative results in its clinical transfer has motivated us to focus on the Bezlotoxumab antibody, still in clinical trials. Within the second work package "WP2.- In vivo evaluation of new radiotracers for the detection of C. difficile by immunoPET" we have started with the tests to fine-tune the animal model within "WP2.1.- Validation of the time course of C. difficile infection in mice". Although the model has shown a slight infection in the target tissue, confirmed not only by visual evaluation of the tissue but also by histology with HyE staining, we are currently modifying the inoculum and preconditioning conditions of the animals to have a more reproducible model similar to the clinical scenario.
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