Harnessing cyanine reactivity to prepare novel fluorophores for surgical imaging applications

Existing fluorescent probes derive from a small set of core scaffolds initially developed for various abiological dye applications and subsequently applied for biomedical research with minimal synthetic modification. Consequently, there exists a significant opportunity to develop molecules specifically tailored for use in surgical imaging applications. Cyanine fluorophores are among the most broadly used fluorescent probes, despite poor chemical stability and modest photon output. To address these limitations, we develop new synthetic transformations that modify the core polymethine chromophore unit. This chemistry has been applied to develop probes with rapid and exclusive renal or hepatobiliary clearance for abdominal surgery applications. Additionally, we have extensively examined the role of probe chemistry on tumor targeting of monoclonal antibody (mAb) conjugates. We also designed cyclizing variants with tunable solvent-sensitive properties that enable efficient no-wash live cell imaging of intracellular targets. Overall, these efforts involve a feedback loop between chemical studies focused on the design and synthesis of novel compounds and in vivo imaging applications.