Small-Animal PET of Melanocortin 1 Receptor Expression Using a 18F-Labeled ?±-Melanocyte-Stimulating Hormone Analog

摘要

id="p-1">18F-Labeled small synthetic peptides have emerged as attractive probes for imaging various molecular targets with PET. The ?±-melanocyte-stimulating hormone (?±-MSH) receptor (melanocortin type 1 receptor [MC1R]) is overexpressed in most murine and human melanomas. It is a promising molecular target for diagnosis and therapy of melanomas. However, 18F compounds have not been successfully developed for imaging the MC1R. >Methods: In this study, an ?±-MSH analog, Ac-Nle-Asp-His- class="sc">d-Phe-Arg-Trp-Gly-Lys-NH₂ (NAPamide), was radiolabeled with N-succinimidyl-4-18F-fluorobenzoate (18F-SFB). The resulting radiopeptide was evaluated as a potential molecular probe for small-animal PET of melanoma and MC1R expression in melanoma xenografted mouse models. >Results: The binding affinity of 19F-SFBa?’conjugated NAPamide, 19F-FB-NAPamide, was determined to be 7.2 ?± 1.2 nM (mean ?± SD) using B16/F10 cells and 125I-(Tyr2)-[Nle4, class="sc">d-Phe7]-?±-MSH [125I-(Tyr2)-NDP] as a radioligand. The biodistribution of 18F-FB-NAPamide was then investigated in C57BL/6 mice bearing subcutaneous murine B16/F10 melanoma tumors with high expression of MC1Rs and Fox Chase Scid mice bearing human A375M melanoma with a relatively low number of MC1R receptors. Biodistribution experiments showed that tumor uptake values (percentage injected dose per gram of tumor [%ID/g]) of 18F-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 ?±-MSH peptide (P 0.05), indicating that 18F-FB-NAPamide specifically recognizes the MC1R in living mice. Small-animal PET of 18F-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: 18F-FB-NAPamide is a promising molecular probe for ?±-MSH receptor-positive melanoma PET and warrants further study.