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

Zhen Cheng, Lan Zhang, Edward Graves, Zhengming Xiong, Mangal Dandekar, Xiaoyuan Chen, Sanjiv Sam Gambhir

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63 Scopus citations


18F-Labeled small synthetic peptides have emerged as attractive probes for imaging various molecular targets with PET. The α-melanocyte- stimulating hormone (α-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 α-MSH analog, Ac-Nle-Asp-His-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-SFB-conjugated NAPamide, 19F-FB-NAPamide, was determined to be 7.2 ± 1.2 nM (mean ± SD) using B16/F10 cells and 125l-(Tyr2)-[Nle4,D-Phe7]- α-MSH [125l-(Tyr2)-NDP] as a radioligand. The biodistribution of 18F-FB-NAPamide was then investigated in C57BL76 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 α-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 α-MSH receptor-positive melanoma PET and warrants further study.

Original languageEnglish (US)
Pages (from-to)987-994
Number of pages8
JournalJournal of Nuclear Medicine
Issue number6
StatePublished - Jun 2007


  • F
  • Imaging
  • Melanoma
  • PET
  • α-melanocyte-stimulating hormone


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