Effects of Amino Acids on Melanoma Targeting and Clearance Properties of Tc-99m-Labeled Arg-X-Asp-Conjugated α-Melanocyte Stimulating Hormone Peptides
| Autor: | Adam M. Flook, Jianquan Yang, Yubin Miao |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Biodistribution
Melanocyte-stimulating hormone Melanoma Experimental Antineoplastic Agents Peptide Conjugated system Article Mice Drug Discovery medicine Animals Tissue Distribution Amino Acids chemistry.chemical_classification Kidney Molecular Structure Staining and Labeling Extramural Melanoma Technetium medicine.disease Molecular biology Amino acid Mice Inbred C57BL medicine.anatomical_structure chemistry Biochemistry alpha-MSH Molecular Medicine Oligopeptides |
| Zdroj: | Journal of Medicinal Chemistry. 56:8793-8802 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm4012356 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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