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G1 1


The major goal of this project is to design multifunctional radioimmunoconjugates for the targeting of tumor endothelial marker 1 (TEM1/endosialin), a receptor overexpressed in several human cancers with minimal expression in normal tissues. For this purpose, Tb radioisotopes produced at the MEDICIS facility in CERN will be used. Terbium is an excellent candidate for theranostic applications possessing four clinically relevant radioisotopes (149Tb, 152Tb, 155Tb and 161Tb) for imaging and therapy. The final conjugates will be obtained by in vivo click reactions between macrocyclic Tb radiocomplexes carrying a tetrazine moiety and antibody fragments functionalized with trans-cyclooctene (TCO), expecting to reduce the systemic radiation exposure of the patients while maximizing the therapeutic efficacy. As a first step, we succeeded on the 125I-labelling of a small panel of TEM1 targeted antibody fragments and evaluated their specific TEM1 targeting ability, which allowed us to select the best candidates for further studies with the Tb radioisotopes.