Molecular imaging of malignant melanoma using a 18F-labeled metallopeptide

Objectives Melanocortin 1 receptor (MC1R) can serve as an attractive molecular target of melanoma imaging and therapy. A transition metal rhenium cyclized-MSH peptide, ReCCMSH (Arg¹¹), has shown high in vitro binding affinity to MC1R and excellent in vivo targeting profiles. We hypothesized that ReCCMSH (Arg¹¹) can be a super platform for PET imaging of melanoma MC1R expression.

Methods The metallopeptide, Ac-d,Lys-ReCCMSH (Arg¹¹) was synthesized using solid phase peptide synthesis chemistry and rhenium cyclization reaction. The resulting peptides were then conjugated with N-succinimidyl-4-[¹⁸F]fluorobenzoate. The ¹⁸F labeled metallopeptides were evaluated by in vitro receptor binding assay, in vivo biodistribution and μPET.

Results Two isomers of rhenium cyclized α-MSH peptides, Ac-d,Lys-ReCCMSH (Arg¹¹)-pk1 and pk2, were identified and purified by HPLC. The binding affinities of both isomers as well as their fluorinated counterparts were about 10nM. Shown by biodistribution and μPET studies, both isomers showed moderate tumor uptakes in B16/F10 model with high MC1R expression, while lower tumor uptakes in A375M model with low MC1R expression. It was also observed that pk1 displayed much less uptakes in kidneys compared with pk2. Furthermore, co-injection of 300 µg α-MSH analog could inhibit the tumor uptake.

Conclusions With great translational potentials, the radiofluorinated metallopeptide, Ac-d,Lys-ReCCMSH (Arg¹¹) successfully and specifically images melanoma and MC1R expression in mice.