Development of a Dual-Modal PET/NIR-II Probe of Urofollitropin for Enhanced Follicle-Stimulating Hormone Receptor-Targeted Imaging in Diverse Tumors

The overexpression of follicle-stimulating hormone receptor (FSHR) in diverse tumors, with low or no expression in normal tissues, makes it a promising target for cancer diagnosis and therapy. Urofollitropin (uFSH), a highly purified form of FSH extracted from the urine of postmenopausal women, is widely used in treating infertility or hypogonadotropic hypogonadism through specifically binding to FSHR expressed on ovaries or granulosa cells in the clinic. Given the specific binding between uFSH and FSHR, the uFSH-derived probe may serve as a potential tool for diagnosing diverse tumors. Therefore, in the present study, using uFSH as the precursor, we developed a dual-modal PET/NIR-II probe named ⁶⁴Cu-NODAGA-uFSH-CH1055 and studied its binding specificity to FSHR in diverse cancers <i>in vitro</i> and <i>in vivo</i>. <i>In vitro</i> cell assays revealed significantly lower fluorescence in the blocking group than in the unblocking group in U87-MG, HT-29, 143B, and PC-3 tumor cells (<i>p</i> < 0.05). Both <i>in vivo</i> PET/CT and NIR-II imaging demonstrated clear tumor visualization. The U87-MG tumors had the highest radioactive uptake (1.80% ± 0.23% ID/g), followed by HT-29 (1.25% ± 0.23% ID/g), 143B (0.98% ± 0.02% ID/g), and PC-3 (0.75% ± 0.11% ID/g) (<i>p</i> = 0.024). The same fluorescence signal intensity trend in diverse tumors was found in the NIR-II images, which was consistent with the FSHR expression detected by Western blotting. Both i<i>n vitro</i> and <i>in vivo</i> assays showed the specific FSHR-targeting capability of ⁶⁴Cu-NODAGA-uFSH-CH1055 in diverse tumors, indicating that the uFSH-based dual-modal probe has the potential for the noninvasive visualization of various tumors through PET/CT and NIR-II imaging.