Peptides play decisive roles in the skin, ranging from host defense responses to various forms of neuroendocrine regulation of cell and organelle function. Synthetic
peptides conjugated to
radionuclides or
photosensitizers may serve to identify and treat skin
tumors and their metastatic forms in other organs of the body. In the introductory part of this review, the role and interplay of the different
peptides in the skin are briefly summarized, including their potential application for the management of frequently occurring
skin cancers. Special emphasis is given to different targeting options for the treatment of
melanoma and melanotic lesions.
Radionuclide Targeting: α-
Melanocyte-stimulating hormone (α-
MSH) is the most prominent
peptide for targeting of
melanoma tumors via the
G protein-coupled
melanocortin-1 receptor that is (over-)expressed by
melanoma cells and melanocytes. More than 100 different linear and cyclic analogs of α-
MSH containing
chelators for 111In, 67/68Ga, 64Cu, 90Y, 212Pb, 99mTc, 188Re were synthesized and examined with experimental animals and in a few clinical studies. Linear Ac-Nle-Asp-His-D-Phe-Arg-Trp-Gly-Lys-NH2 (NAP-
amide) and Re-cyclized Cys- Cys-Glu-His-D-Phe-Arg-Trp-Cys-Arg-Pro-Val-NH2 (Re[Arg11]CCMSH) containing different
chelators at the N- or C-terminus served as lead compounds for
peptide drugs with further optimized characteristics. Alternatively,
melanoma may be targeted with radiopeptides that bind to
melanin granules occurring extracellularly in these
tumors.
Photosensitizer targeting: A more recent approach is the application of
photosensitizers attached to the
MSH molecule for targeted
photodynamic therapy using LED or coherent
laser light that specifically activates the
photosensitizer. Experimental studies have demonstrated the feasibility of this approach as a more gentle and convenient alternative compared to
radionuclides.