Sprayable pH-sensitive near-infrared fluorophore for rapid, bright, specific, and safe visualization of human thyroid cancer in orthotopic mouse models.

[BACKGROUND] Surgery is the primary treatment for thyroid cancer. However, incomplete resection of thyroid cancer can result in local, regional, and distant recurrences that are life threatening. We hypothesized that a topically applied, pH-sensitive near-infrared fluorophore in spray form (PH10) could offer rapid labeling of thyroid tumors, enabling better visualizion of the tumor and its margins.

[METHODS] Cellar uptake inhibition and cytotoxicity studies using PH10 were performed on TPC-1 papillary and TT medullary thyroid cancer cells. Subcutaneous or orthotopic tumors were established by injecting TPC-1 cells in the flanks or thyroid glands of nude mice, respectively, and sprayed with PH10. Fluorescence of the tumor was compared to surrounding tissues. Tumors were harvested for pathologic analysis.

[RESULTS] The organic anion transporter peptide mediated uptake of PH10 in TPC-1 and TT cells was determined. PH10 exhibited an IC50 value of 13.18 and 17.28 μM in TPC-1 and TT cells, respectively. Both subcutaneous and orthotopic tumors displayed strong near-infrared fluorescence upon spraying PH10 at a concentration of 10 μM on the tumor sites, within 1 minute, contrasting with surrounding tissues. The effective PH10 dose for tumor visualization was well below the IC50. The average tumor to background ratios were 5.5 (±1.47) for subcutaneous tumors (n = 5) and 9.4 (±2.59) for orthotopic tumors (n = 5). Hematoxylin and eosin staining confirmed the tumor characteristics.

[CONCLUSION] The pH-sensitive near-infrared fluorophore PH10 brightly, rapidly, specifically, and safely labeled thyroid cancer in mouse models by spraying, demonstrating future clinical promise as a useful agent for improved visualization of thyroid cancer.