Melanoma imaging using 111In-, 86Y- and 68Ga-labeled CHX-A-Re(Arg11)CCMSH

Introduction: A novel alpha-melanocyte-stimulating hormone peptide analog CHX-A-Re(Arg(11))CCMSH, which targeted the melanocortin-1 receptor (MCI-R) overexpressed on melanoma cells, was investigated for its biodistribution and tumor imaging properties Methods: The metal bifunctional chelator CHX-A '' was conjugated to the melanoma targeting peptide (Arg(11))CCMSH and cyclized by Re incorporation to yield CHX-A ''-Re(Arg(11))CCMSH. CHX-A ''-Re(Arg(11))CCMSH was labeled with In-111, Y-86 and Ga-68, and the radiolabeled peptides were examined in B16/F1 melanoma-bearing mice for their pharmacokinetic as well as their tumor targeting properties using small Results: The radiolabeling efficiencies of the In-111-, Y-86- and Ga-68-labeled CHX-A ''-Re(Arg(11))CCMSH peptides were >95%, resulting in specific activities of 4.44, 3.7 and 1.85 MBq/mu g, respectively. Tumor uptake of the In-111-, Y-86- and Ga-68-labeted peptides was rapid with 4.17 +/- 0.94, 4.68 +/- 1.02 and 2.68 +/- 0.69 %ID/g present in the tumors 2 h postinjection, respectively. Disappearance of radioactivity from the normal organs and tissues was rapid with the exception ofthe kidneys. Melanorna tuniors were iniaged with all three radiolabeled peptides 2 h postinjection. MC1-R-specific uptake was confirmed by competitive receptor blocking studies. Conclusions: Melanoma tumour uptake and imaging was exhibited by the In-111-, Y-86- and Ga-68-labeled Re(Arg(11))CCMSH peptides, although the tumor uptake was moderated by low specific activity. The facile radiolabeling properties of CHX-A ''-Re(Arg(11))CCMSH allow it to be employed as a melanoma imaging agent with little or no purification after In-111, Y-86 and Ga-68 labeling. (C) 2009 Elsevier Inc. All rights reserved.