WazaGaY: An Innovative Aza-BODIPY-Derived Near-Infrared Fluorescent Probe for Enhanced Tumor Imaging

  • J Med Chem. 2024 Sep 26;67(18):16635-16648. doi: 10.1021/acs.jmedchem.4c01435.
Mohamed Bendellaa  1 ,  Charlotte Cave  2 ,  Amélie Godard  2 ,  Fabien Dalonneau  1 ,  Annika Sickinger  3 ,  Christine Goze  2 ,  Olivier Maury  3 ,  Pierre Le Gendre  2 ,  Ewen Bodio  2  4  5 ,  Benoit Busser  1  5  6 ,  Lucie Sancey  1
Affiliations
  • 1. Université Grenoble Alpes, INSERM U1209, CNRS UMR 5309, Institute for Advanced Biosciences (IAB), Grenoble 38000, France.
  • 2. Institut de Chimie Moléculaire de l'Université de Bourgogne, Université de Bourgogne, CNRS UMR 6302, Dijon 21078, France.
  • 3. CNRS, ENS de Lyon, CNRS, LCH, UMR 5182, Lyon F-69342, France.
  • 4. Nantes Université, CNRS, CEISAM, UMR 6230, Nantes F-44000, France.
  • 5. Institut Universitaire de France (IUF), Paris 75005, France.
  • 6. Grenoble Alpes University Hospital (CHUGA), Grenoble 38043, France.
PMID: 39289797 DOI: 10.1021/acs.jmedchem.4c01435
Abstract

Aza-BODIPYs represent a class of fluorophores in which the π-conjugated system is rigidified and stabilized by a boron atom. A promising strategy to enhance their fluorescence properties involves replacing the boron atom with a metal ion. Here, we describe the synthesis and characterization of a water-soluble derivative where the metal is a gallium(III) ion, termed WazaGaY (water-soluble aza-GaDIPY). Water solubility is ensured by two ammonium substituents, inducing a bathochromic shift and a significant increase in quantum yield compared to that of the dimethylamino analog. The cellular behavior of WazaGaY-1 was observed across different tumor cells. In vivo, the distribution and safety profiles were determined, and tumor uptake was assessed in various tumor types. Following intravenous injection, WazaGaY-1 enabled clear discrimination of tumors engrafted subcutaneously in mice with high tumor-to-muscle ratios (ranging from 7 to 20), even in the absence of specific conjugation. Its potential as a contrast agent for fluorescence-guided surgery was confirmed.

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