Bright, stable, heptamethine cyanine fluorophores for in vivo imaging
Thursday, September 13, 2018 — Poster Session III
- MP Luciano
- RR Nani
- GM Kline
- MJ Schnermann
Near-infrared (NIR) fluorophores enable the in vivo visualization of biological processes and various disease states. Improving the physical and chemical properties of NIR fluorophores is essential to realizing the potential of the various types of biomedical imaging. The commercially available fluorophore IR-Dye800CW is frequently used in preclinical and clinical studies for fluorescence guided surgery (FGS) and its derivatives have been used in a variety of basic science applications. However, its instability toward glutathione and the cellular proteome complicate its use as a contrast agent for in vivo imaging. We have developed a novel class of NIR fluorescent heptamethine cyanine dyes to address the limitations of IR-Dye800CW. These dyes bear a central C4-O-alkyl linker rather than the C4-O-phenyl linker in IR-Dye800CW, making them more stable to biological nucleophiles. We have prepared novel molecules that are zwitterionic in nature with an even charge distribution. These subtle changes to the substituents of the cyanine core result in dramatic changes to the optical properties and in vivo fate of the free dyes. For example, these dyes are exclusively cleared through the kidney, with negligible liver uptake in mouse, rat and pig models. These properties allow easy visualization of the ureter – a site of frequent injury - during abdominal FGS in a rat model.
Category: Chemical Biology