Repurposing GnRH-A as a Near-Infrared Fluorescent Probe for Diagnosis and Surgical Navigation of Breast Cancer Tumors and Metastases.

Breast cancer, globally the most common cancer in women, presents significant challenges in treatment. Breast-conserving surgery (BCS), a less traumatic and painful alternative to radical mastectomy, not only preserves the breast's appearance but also supports postsurgical functional recovery. However, accurately identifying tumors, precisely delineating margins, and thoroughly removing metastases remain complex surgical challenges, exacerbated by the limitations of current imaging techniques, including poor tumor uptake and low signal contrast. Addressing these challenges, our study developed a series of GnRHR-targeted probes (YQGN- n ) for fluorescence imaging and surgical navigation of breast cancer through a drug repositioning strategy. Notably, YQGN-7, with its high cellular affinity ( K d of 217.8 nM), demonstrates exceptional selectivity and specificity for breast cancer tumors, surpassing traditional imaging agents like ICG in tumor uptake and pharmacokinetic properties. Furthermore, YQGN-7's effectiveness in surgical navigation, both for primary breast tumors and metastases, highlights its potential as a revolutionary tool in BCS.