PET of Malignant Melanoma Using 18F-Labeled Metallopeptides

摘要: Melanocortin type 1 receptor (MC1R), also known as α-melanocyte–stimulating hormone (α-MSH) receptor, is an attractive molecular target for melanoma imaging and therapy. An 18F-labeled linear α-MSH peptide (18F-FB-Ac-Nle-Asp-His-d-Phe-Arg-Trp-Gly-Lys-NH2 [NAPamide]) shows promising properties but with only moderate tumor uptake retention. A transition metal rhenium-cyclized peptide, ReO[Cys3,4,10,d-Phe7,Arg11]α-MSH3–13 (ReCCMSH(Arg11)), has shown high in vitro binding affinity to MC1R excellent vivo melanoma-targeting profiles when labeled radiometals. Therefore, we hypothesized that ReCCMSH(Arg11) could be a good platform the further development of probe PET MC1R-positive malignant melanoma. Methods: In this study, metallopeptide Ac-d-Lys-ReCCMSH(Arg11) was synthesized using conventional solid-phase synthesis chemistry rhenium cyclization reaction. The resulting peptides were then N-succinimidyl-4-18F-fluorobenzoate (18F-SFB). metallopeptides tested their affinities, biodistribution, properties. Results: Both isomers Ac-d-Lys-ReCCMSH(Arg11), named RMSH-1 RMSH-2, purified identified by high-performance liquid chromatography. affinities RMSH-2 respective 19F-SFB–conjugated (19F-FB-RMSH-1 19F-FB-RMSH-2) all determined within nanomolar range. showed B16F10 murine model, expression, much lower A375M human xenografted mice, indicating low expression. 18F-FB-RMSH-1, compared 18F-FB-RMSH-2, displayed more favorable performance terms slightly higher uptakes accumulations kidney liver at 2 h after injection. Small-animal 18F-FB-RMSH-1 -2 mice bearing tumors quality. As expected, poorer tumor–to–normal organ contrasts observed model than model. better retention did 18F-FB-NAPamide. Conclusion: Specific targeting successfully achieved preclinical models Thus, radiofluorinated tumors.