A Novel Estrogen Receptor α-Targeted Near-Infrared Fluorescent Probe for in Vivo Detection of Breast Tumor

The ability to detect breast cancer early in its progression is essential to improve patient survival and quality of life. The noninvasive and dynamic imaging and functional assessments of estrogen receptor-alpha (ERα), which is commonly expressed at high levels in breast cancer, are important for effective diagnosis and treatment. Hence, the development of a specific ERα-targeted probe is a major research goal. To that end, in the present study, we created a novel near-infrared (NIR) fluorescent probe, IRDye800CW–E2, for targeted ERα imaging in breast-tumor-bearing mice. IRDye800CW–E2 consisted of a cyanine dye IRDye800CW as the NIR fluorophore and the E2 analogue ethinyl estradiol amine as an ERα targeting ligand. The ethinyl estradiol amine was initially labeled with fluorescein isothiocyanate (FITC) to evaluate the binding specificity to human breast-tumor cells in vitro. Flow chamber and in vitro confocal laser endomicroscopy imaging experiments demonstrated that FITC–E2 was specifically taken up by MCF-7 cells. Furthermore, NIR fluorescence imaging revealed the ability of IRDye800CW–E2 to rapidly target tumors and to achieve good contrast between tumors and background signal 4–48 h postinjection. The fluorescent signal of IRDye800CW–E2 in tumors was successfully blocked by the coinjection of the endogenous ERα-ligand 17β-estradiol (E2) and the probe. Ex vivo fluorescent imaging further confirmed high uptake of the probe by tumors. These results indicated that IRDye800CW–E2 has great potential as an ERα-targeted imaging probe for early breast-tumor detection and has potential for clinical translation.