NIR-II Aza-BODIPY Dyes Bioconjugated to Monoclonal Antibody Trastuzumab for Selective Imaging of HER2-Positive Ovarian Cancer

• Published in: Journal of medicinal chemistry 2023-04, Vol.66 (7), p.5185-5195
• Main Authors: Godard, Amélie, Kalot, Ghadir, Privat, Malorie, Bendellaa, Mohamed, Busser, Benoit, Wegner, K. David, Denat, Franck, Le Guével, Xavier, Coll, Jean-Luc, Paul, Catherine, Bodio, Ewen, Goze, Christine, Sancey, Lucie
• Format: Article
• Language: English
• Subjects: Antibodies, Monoclonal - therapeutic use; Bioengineering; Cancer; Chemical Sciences; Female; Fluorescent Dyes; Humans; Imaging; Life Sciences; Medicinal Chemistry; Ovarian Neoplasms - diagnostic imaging; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - metabolism; Trastuzumab - therapeutic use
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/acs.jmedchem.3c00100

Using fluorescence-guided surgery (FGS) to cytoreductive surgery helps achieving complete resection of microscopic ovarian tumors. The use of visible and NIR-I fluorophores has led to beneficial results in clinical trials; however, involving NIR-II dyes seems to outperform those benefits due to the deeper tissue imaging and higher signal/noise ratio attained within the NIR-II optical window. In this context, we developed NIR-II emitting dyes targeting human epidermal growth factor receptor 2 (HER2)-positive ovarian tumors by coupling water-soluble NIR-II aza-BODIPY dyes to the FDA-approved anti-HER2 antibody, namely, trastuzumab. These bioconjugated NIR-II-emitting dyes displayed a prolonged stability in serum and a maintained affinity toward HER2 in vitro. We obtained selective targeting of HER2 positive tumors (SKOV-3) in vivo, with a favorable tumor accumulation. We demonstrated the fluorescence properties and the specific HER2 binding of the bioconjugated dyes in vivo and thus their potential for NIR-II FGS in the cancer setting.