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Effects of amino acids on melanoma targeting and clearance properties of Tc-99m-labeled Arg-X-Asp-conjugated α-melanocyte stimulating hormone peptides.

Abstract
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.
AuthorsAdam M Flook, Jianquan Yang, Yubin Miao
JournalJournal of medicinal chemistry (J Med Chem) Vol. 56 Issue 21 Pg. 8793-802 (Nov 14 2013) ISSN: 1520-4804 [Electronic] United States
PMID24131154 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Amino Acids
  • Antineoplastic Agents
  • Oligopeptides
  • alpha-MSH
  • Technetium
Topics
  • Amino Acids (chemistry, pharmacokinetics, pharmacology)
  • Animals
  • Antineoplastic Agents (chemistry, pharmacokinetics, pharmacology)
  • Melanoma, Experimental (drug therapy, pathology)
  • Mice
  • Mice, Inbred C57BL
  • Molecular Structure
  • Oligopeptides (chemistry)
  • Staining and Labeling
  • Technetium (chemistry)
  • Tissue Distribution
  • alpha-MSH (chemistry, pharmacokinetics, pharmacology)

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