Targeted NIR-I and NIR-II fluorescent dyes for intraoperative lung cancer visualization

Our lab focuses on translation of near-infrared (NIR) fluorophores for fluorescence-guided surgery of non-small cell lung cancer (NSCLC). Our most advanced dye, JAS239 targets choline kinase (ChoKα), a critical enzyme in lipid biosynthesis that is overexpressed in 60% of NSCLCs and associated with high tumor grade and poor outcome. We completed a veterinary clinical trial of JAS239 in 20 canine patients with spontaneous NSCLC. Pathology revealed clean tumor margins in 18/19 patients with the close margin occurring in a predominantly necrotic tumor. A pre-IND has been submitted to the FDA, we are currently conducting the IND-enabling studies necessary for Phase-I human clinical trials. A second class of actvatable fluorophores target cytosolic phospholipase A2 (cPLA2), a signaling enzyme involved in prostaglandin metabolism and overexpressed in 45% of NSCLC. DDAO-arachidonate (DDAO-A) is activated by cPLA2 in NSCLC relative to normal tissues in mouse models, ex vivo in canine and human tissues. Following toxicology, DDAO-A will enter veterinary clinical trials in canine patients. Our most recent studies involve synthesis of quinocyanines (QCys), a new class of short-wave infrared (SWIR) fluorophores. QCys are low molecular weight (<530 Da), with emission ~1000 nm. QCys showed superior tissue penetration and resolution compared to NIR-I dyes in phantoms and in mice, allowing for high-resolution vascular imaging and clearer imaging of internal organs. In tumor models and tissues QCys show low autofluorescence and TBRs >12. The ability of QCys to reach significant depths and provide high-resolution, high TBR images positions them as promising candidates for surgical imaging.