TY - JOUR A1 - Chazeau, E. A1 - Pipier, A. A1 - Wegner, Karl David A1 - Ghiringhelli, F. A1 - Sancey, L. A1 - Paul, C. A1 - Goze, C. T1 - NIR-II aza-BODIPY Platform for the Development of a Fluorescent Antibody Drug Conjugate N2 - 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. KW - NIR-II KW - Fluorescence KW - Quality assurance KW - Antibody drug conjugate KW - In vivo imaging PY - 2025 DO - https://doi.org/10.1021/acs.jmedchem.4c02777 VL - 68 IS - 7 SP - 7232 EP - 7242 PB - ACS Publications AN - OPUS4-63025 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER -