化学
荧光
示踪剂
生物物理学
药理学
癌症研究
量子力学
医学
生物
物理
核物理学
作者
Malorie Privat,Aurélie Massot,François Hermetet,Hassan Al Sabea,Cindy Racoeur,Nesrine Mabrouk,Marine Cordonnier,Mathieu Moreau,Bertrand Collin,Ali Bettaı̈eb,Franck Denat,Ewen Bodio,Pierre-Simon Bellaye,Christine Goze,Catherine Paul
标识
DOI:10.1021/acs.jmedchem.3c02120
摘要
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.
科研通智能强力驱动
Strongly Powered by AbleSci AI