Background: 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
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.