Synthesis, Characterization, and Initial Biological Evaluation of [^99mTc]Tc‐Tricarbonyl‐labeled DPA‐α‐MSH Peptide Derivatives for Potential Melanoma Imaging

Abstract

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-NH ) with and without linkers was conjugated with 5-(bis(pyridin-2-ylmethyl)amino)pentanoic acid (DPA-COOH) and labeled with [ Tc]Tc-tricarbonyl by two methods. With the one-pot method the labeling was faster than with the two-pot method, while obtaining similarly high yields. Negligible trans-chelation and high stability in physiological solutions was determined for the [ Tc]Tc-tricarbonyl-peptide conjugates. Coupling an ethylene glycol (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 homogenates. Preliminary in vivo studies with one of the [ Tc]Tc-tricarbonyl-peptide conjugates showed good stability in blood and both renal and hepatobiliary excretion. Biodistribution was performed on healthy rats to gain initial insight into the potential relevance of the Tc-labeled peptides for in vivo imaging.

Neuroendocrine Factors in Melanoma Pathogenesis

“…There is also a diagnostic value of α-MSH in the management of melanoma which is worth mentioning. Labeling α-MSH with 99mTc offers high sensitivity for the diagnosis of melanoma, in both primary tumor and involved lymph nodes [ 190 , 191 ].…”

Strategic Evaluation of the Traceless Staudinger Ligation for Radiolabeling with the Tricarbonyl Core

“…For the following radiolabeling with technetium-99m, a two-step procedure was applied, first to generate the 99m Tc(CO) 3 species from the 99m Tc-pertechetate solution using a tricarbonyl kit and secondly to perform the final complexation with the DPA-containing ligands [36]. For this purpose, approximately 500 MBq of [ 99m Tc]TcO 4…”

Preparation, Characterization, and Radiolabeling of Anti‐HER2 scFv With Technetium Tricarbonyl and Stability Studies

“…They also exhibit enhanced pharmacokinetic properties and rapidly clear from the bloodstream [16]. Therefore, in comparison with intact antibodies, scFvs are preferred for imaging studies [17,18]. They can be radiolabeled with short half-life radioisotopes for nuclear imaging such as positron emission tomography (PET) or single photon emission computed tomography (SPECT) [19].…”