The purpose of this study was to examine the effects of
amino acids on
melanoma targeting and clearance properties of new (99m)Tc-labeled Arg-X-Asp-conjugated α-
melanocyte stimulating hormone (α-
MSH)
peptides. RSD-Lys-(Arg(11))CCMSH {c[Arg-Ser-Asp-DTyr-
Asp]-Lys-
Cys-Cys-Glu-His-dPhe-Arg-Trp-Cys-
Arg-Pro-Val-NH2}, RNleD-Lys-(Arg(11))CCMSH, RPheD-Lys-(Arg(11))CCMSH, and RdPheD-Lys-(Arg(11))CCMSH
peptides were synthesized and evaluated for their melanocortin-1 (
MC1) receptor binding affinities in B16/F1
melanoma cells. The biodistribution of (99m)Tc-RSD-Lys-(Arg(11))CCMSH, (99m)Tc-RFD-Lys-(Arg(11))CCMSH, and (99m)Tc-RfD-Lys-(Arg(11))CCMSH were determined in B16/F1
melanoma-bearing C57 mice. The substitution of Gly with Ser, Phe, and dPhe increased the
MC1 receptor binding affinities of the
peptides, whereas the substitution of Gly with Nle decreased the
MC1 receptor binding affinity of the
peptide. (99m)Tc-RSD-Lys-(Arg(11))CCMSH exhibited the highest
melanoma uptake (18.01 ± 4.22% ID/g) and the lowest kidney and liver uptake among these (99m)Tc-peptides. The B16/F1
melanoma lesions could be clearly visualized by SPECT/CT using (99m)Tc-RSD-Lys-(Arg(11))CCMSH as an imaging probe. It is desirable to reduce the renal uptake of (99m)Tc-RSD-Lys-(Arg(11))CCMSH to facilitate its potential therapeutic application.