Fiche projet
Année
2025
Appel à projets
Appel à projets « Soutien à l'émergence de projets transfrontaliers » (Cancéropôle Est)
Acronyme
ProstaTerb
Resumé
The aim of the transdisciplinary project ProstaTerb is to evaluate in vitro and in vivo 161Tb-labeled immunoconjugates specifically designed for the treatment of metastasized castration-resistant prostate cancer (mCRPC). Currently, 177Lu(DOTA) conjugates are the state of the art in targeted radionuclide therapy (TRT) of mCRPC. The originality of our constructs stems from the site-specific conjugation of open-chain chelators of tetrapodal or linear topologies, forming rapidly stable and inert complexes at room temperature to a novel and proprietary monoclonal antibody (mAb) developed by a French biotech SME that specifically binds to the prostate-specific membrane antigen (PSMA) receptors. In that respect, they differ from the classical bioconjugates, which at very few exceptions incorporate all a macrocyclic DOTA ligand, reputed to react very slowly with lanthanides according to a multistep mechanism. Therefore, peptides are usually used as biological vectors for DOTA-based radiopharmaceuticals, as they withstand the high-temperature labeling conditions required to fully encapsulate the metal center. To avoid the denaturation of the mAb at the labeling stage or the in vivo release of the partially encapsulated radionuclide (RN) by DOTA–mAb constructs labeled at near physiological temperatures, new chelators are sought. Following a molecular engineering approach, a series of original bifunctional chelators (BFC) has been prepared and their coordination properties of natTb3+ established. The thereby identified hits will be bioconjugated using a site specific technique developed by our SME partner. Radiolabeling with 161Tb, in vitro stability tests, immunoreactivity assays with the appropriate cell line, and preclinical in vivo evaluation in mice will be performed by our Swiss partner at CHUV in Lausanne.
Avec Dr VIERTL David (Centre hospitalier universitaire Vaudois, Lausanne, Suisse)
Partenaires
Territoire
Alsace
Mots clés
Terbium-161, immunotheranostic radiopharmaceutical, prostate cancer, targeted radionuclide therapy, synthesis of bifunctional chelators, bioconjugation, preclinical evaluation
