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Journal of Medicinal Chemistry

  • Biochimie et nanosenseurs
  • Oncologie
  • Pharmacologie

Development of an Immuno-SPECT/Fluorescent Bimodal Tracer Targeting Human or Murine PD-L1 on Preclinical Models

Auteurs Malorie Privat, Aurélie Massot, François Hermetet, Hassan Al Sabea, Cindy Racoeur, Nesrine Mabrouk, Marine Cordonnier, Mathieu Moreau, Bertrand Collin, Ali Bettaieb, Franck Denat, Ewen Bodio, Pierre-Simon Bellaye, Christine Goze, Catherine Paul

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 [111In]-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. In vitro, these bimodal mAbs showed a good stability and affinity for PD-L1. In vivo, 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.

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