Development of an Immuno-SPECT/Fluorescent Bimodal Tracer Targeting Human or Murine PD-L1 on Preclinical Models.
Fiche publication
Date publication
janvier 2024
Journal
Journal of medicinal chemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BETTAIEB Ali, Dr HERMETET François, Pr PAUL Catherine, Pr DENAT Franck, Dr COLLIN Bertrand, Dr BELLAYE Pierre-Simon
Tous les auteurs :
Privat M, Massot A, Hermetet F, Al Sabea H, Racoeur C, Mabrouk N, Cordonnier M, Moreau M, Collin B, Bettaieb A, Denat F, Bodio E, Bellaye PS, Goze C, Paul C
Lien Pubmed
Résumé
Detection of biomarkers to diagnose, treat, and predict the efficacy of cancer therapies is a major clinical challenge. Currently, biomarkers such as PD-L1 are commonly detected from biopsies, but this approach does not take into account the spatiotemporal heterogeneity of their expression in tumors. A solution consists in conjugating monoclonal antibodies (mAbs) targeting these biomarkers with multimodal imaging probes. In this study, a bimodal [In]-DOTA-aza-BODIPY probe emitting in the near-infrared (NIR) was grafted onto mAbs targeting murine or human PD-L1 either in a site-specific or random manner. , these bimodal mAbs showed a good stability and affinity for PD-L1. , they targeted specifically PD-L1 and were detected by both fluorescence and SPECT imaging. A significant benefit of site-specific conjugation on glycans was observed compared to random conjugation on lysine. The potential of this bimodal agent was also highlighted, thanks to a proof of concept of fluorescence-guided surgery in a human PD-L1+ tumor model.
Référence
J Med Chem. 2024 01 25;: