Fluorescence Discrimination of Cancer from Inflammation by Selective Targeting Folate Receptor α

We present NY-07, an antifolate dye conjugate capable of intrasurgical discrimination between inflammatory and cancerous tissues. This capability addresses a longstanding problem in fluorescence-guided surgery, where the current FDA-approved probes exhibit false-positive rates of 25-68% due to nonspecific accumulation in inflammatory tissue, leading to unnecessary tissue resection and increased surgical morbidity. NY-07 selectively targets folate receptor α (FRα) overexpressed in tumors while exhibiting 8-fold reduced affinity for folate receptor β (FRβ) predominantly found on inflammatory macrophages (<i>K</i> _d = 61.67 nM vs 486.9 nM). In mouse models, NY-07 achieved a tumor-to-background ratio of 3.23 ± 0.28 with fluorescence signals in tumor tissue significantly exceeding inflammatory areas (<i>p</i> < 0.01). The probe detected submillimeter cancer lesions while avoiding false signals in pneumonia and arthritis models. Co-localization studies using immunohistochemical staining and fluorescence microscopy confirmed that FRα-positive areas in tumor tissue exhibited strong fluorescence intensity, while FRβ-positive areas showed a minimal signal. NY-07 maintained diagnostic imaging windows exceeding 12 days and demonstrated acceptable safety profiles in Phase I clinical trials (CTA: CXHL2401187), having received IND approval from both FDA and NMPA. These results position NY-07 as a strong clinical candidate with the potential to improve surgical precision and reduce false-positive resections.