Small-animal PET of melanocortin 1 receptor expression using a 18F-labeled α-melanocyte-stimulating hormone analog

F-18-Labeled small synthetic peptides have emerged as attractive probes for imaging various molecular targets with PET. The a-melanocyte-stimulating hormone (a-MSH) receptor (melano-cortin type 1 receptor [MC1 R]) is overexpressed in most murine and human melanomas. It is a promising molecular target for diagnosis and therapy of melanomas. However, F-18 compounds have not been successfully developed for imaging the MC1 R. Methods: In this study, an a-MSH analog, Ac-Nle-Asp-His-DPhe-Arg-Trp-Gly-Lys-NH2 (NAPamide), was radiolabeled with N-succinimidyl-4-F-18-fluorobenzoate (F-18-SFB). The resulting radiopeptide was evaluated as a potential molecular probe for small-animal PET of melanoma and MC1 R expression in melanoma xenografted mouse models. Results: The binding affinity of F-19-SFB-conjugated NAPamide,F-19-FB-NAPamide, was determined to be 7.2 +/- 1.2 nM (mean SD) using B16/F10 cells and I-125-(Tyre)-[Nle(4),D-Phe(7)]-alpha-MSH [I-125-(Tyr(2))-NDP] as a radioligand. The biodistribution of F-18-FB-NAPamide was then investigated in C57BU6 mice bearing subcutaneous murine B16/F10 melanoma tumors with high expression of MC1 Rs and Fox Chase Scid mice bearing human A375M melanoma with a relatively low number of MC1 R receptors. Biodistribution experiments showed that tumor uptake values (percentage injected dose per gram of tumor [%ID/g]) of F-18-FB-NAPamide were 1.19 +/- 0.11 %ID/g and 0.46 +/- 0.11 %ID/g, in B16/F10 and A375M xenografted melanoma at 1 h after injection, respectively. Furthermore, the B16/F10 tumor uptake was significantly inhibited by coinjection with excess a-MSH peptide (P < 0.05), indicating that F-18-FB-NAPamide specifically recognizes the MC1 R in living mice. Small-animal PET of F-18-FB-NAPamide in mice bearing B16/F10 and A375M tumors at 1 h after tail vein injection revealed good B16/F10 tumor-to-background contrast and low A375M tumor-to-background ratios. Conclusion: (FFB)-F-18-NAPamide is a promising molecular probe for a-MSH receptor-positive melanoma PET and warrants further study.