sNIR: A novel NIR dye for precision fluorescence-guided surgery

Complete removal of tumors during surgery is essential to minimizing the risk of recurrence, and labeling tumors so that they fluoresce at near-infrared wavelengths can assist surgeons in detecting residual neoplastic tissue intraoperatively. Fluorescent contrast agents currently under clinical investigation are often not cancer cell-specific and suffer from non-specific retention. This drastically compromises tumor-to-background contrast ratios and, thus, the detection of small tumor lesions. Here, we report a novel cyanine dye, “sNIR,” which mediates faster excretion and reduced non-specific binding compared to the commercially available benchmark IRDye800. When conjugated to validated ligands of tumor-associated cell surface markers, only sNIR-based contrast agents enabled high-contrast tumor imaging in murine models. To exemplify sNIR's clinical potential, we focused on meningioma resection - a clinical challenge where microscopic tumor remnants left in the resection bed drive recurrence. Our probe “TATE-sNIR” specifically targets somatostatin receptor subtype 2 (SSTR2), reliably overexpressed in meningiomas. TATE-sNIR binds the target receptor tightly and specifically in vitro and in vivo, enabling clean receptor-mediated imaging in healthy mice and in mice bearing ectopic or orthotopic meningiomas or ectopic pheochromocytomas. A proof-of-concept study in healthy pigs demonstrated the accumulation of TATE-sNIR in the pituitary gland, an expected target organ. The signal was strong enough to be detectable by clinical exoscopes with near-infrared fluorescence imaging capabilities, underscoring TATE-sNIR’s translational potential. With its high labeling precision and efficiency, TATE sNIR holds great potential to visualize microscopic meningioma tumor remnants too small to be detected using the current standard of practice, even during extended surgeries.