Synthesis, characterization and initial biological evaluation of [⁹⁹ᵐTc]Tc-tricarbonyl labeled DPA-α-MSH peptide derivatives for potential melanoma imaging

α-Melanocyte stimulating hormone (α-MSH) derivatives target the melanocortin-1 receptor (MC1R) specifically and selectively. In this study, the α-MSH derived peptide NAP-NS1 (Nle-Asp-His-D-Phe-Arg-Trp-Gly-NH₂) with and without linkers was conjugated with 5-(bis(pyridin-2-yl)methyl)amino)pentanoic acid (DPA-COOH) and labeled with [⁹⁹ᵐTc]Tc-tricarbonyl by two methods. With the one-pot method the labeling was faster than with the two-pots method, however obtaining similarly high yields. Negligible transchelation and high stability in physiological solutions was determined for the [⁹⁹ᵐTc]Tc-tricarbonyl-peptide conjugates. Coupling an ethylenglycol (EG)-based linker increased the hydrophilicity. The peptide derivatives displayed high binding affinity in murine B16F10 melanoma cells as well as in human MeWo and TXM13 melanoma cell homogenate. Preliminary in vivo studies with one of the [⁹⁹ᵐTc]Tc-tricarbonyl-peptide conjugates showed good stability in blood and both a renal and hepatobiliary excretion. Biodistribution was performed on healthy rats to gain initial insights into the potential relevance of the ⁹⁹ᵐTc-labeled peptides for in vivo imaging.