Fiche publication
Date publication
mars 2025
Journal
Journal of medicinal chemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Pr GHIRINGHELLI François
,
Pr PAUL Catherine
Tous les auteurs :
Chazeau E, Pipier A, Wegner KD, Ghiringhelli F, Sancey L, Paul C, Goze C
Lien Pubmed
Résumé
Real-time imaging of antibody-drug conjugates (ADCs) offers valuable insights for assessing tumor targeting specificity, monitoring therapeutic efficacy, and detecting off-target accumulation that may cause adverse effects. To enable precise tracking, we developed a versatile fluorescent platform based on an NIR-II emitting aza-BODIPY dye, which can be site-specifically grafted onto an IgG1 antibody to generate well-defined fluorescent ADCs. As a proof of concept, we synthesized an HER2-targeting trastuzumab immunoconjugate bearing a NIR-II aza-BODIPY fluorophore. The cytotoxic monomethyl auristatin E (MMAE) payload was introduced in the final step, resulting in a trackable and homogeneous ADC suitable for both in vitro and in vivo investigations. The resulting Trastu-azaNIRII-MMAE selectively accumulated in HER2-positive subcutaneous tumors, significantly reducing the tumor growth. Using NIR-II optical imaging, a single injection of the NIR-II-ADC allowed for the detection of the conjugate over a period of more than one month, highlighting its potential for long-term tracking and therapeutic applications.
Référence
J Med Chem. 2025 03 28;:
