The incidence of
malignant melanoma is rising more rapidly than that of any other
cancer in the United States. The
melanocortin 1 receptor (MC1R) is overexpressed in most human
melanoma metastases, thus making it a promising target for imaging and
therapy of
melanomas. We have previously reported the development of a
peptidomimetic ligand with high specificity and affinity for MC1R. Here, we have conjugated near-infrared
fluorescent dyes to the C-terminus of this
ligand via
lysine-mercaptopropionic
acid linkers to generate MC1R specific optical probes (MC1RL-800, 0.4 nM K(i); and MC1RL-
Cy5, 0.3 nM K(i)). Internalization of the imaging probe was studied in vitro by fluorescence microscopy using engineered A375/MC1R cells and B16F10 cells with endogenous MC1R expression. The in vivo
tumor targeting of MC1RL-800 was evaluated by
intravenous injection of probe into nude mice bearing bilateral subcutaneous A375 xenograft
tumors with low MC1R expression and engineered A375/MC1R
tumors with high receptor expression. Melanotic B16F10 xenografts were also studied. Fluorescence imaging showed that the agent has higher uptake values in
tumors with high expression compared to low (p < 0.05), demonstrating the effect of expression levels on image contrast-to-noise. In addition,
tumor uptake was significantly blocked by coinjection of excess NDP-α-
MSH peptide (p < 0.05). In conclusion, the MC1R-specific imaging probe developed in this study displays excellent potential for the intraoperative detection of regional node involvement and for margin detection during
melanoma metastasis resection.