Introduction: A novel alpha-melanocyte-stimulating hormone peptide analog CHX-A''-Re(Arg(11))CCMSH, which targeted the melanocortin-1 receptor (MC1-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 (111)In, (86)Y and (68)Ga, and the radiolabeled peptides were examined in B16/F1 melanoma-bearing mice for their pharmacokinetic as well as their tumor targeting properties using small animal SPECT and PET.
Results: The radiolabeling efficiencies of the (111)In-, (86)Y- and (68)Ga-labeled CHX-A''-Re(Arg(11))CCMSH peptides were >95%, resulting in specific activities of 4.44, 3.7 and 1.85 MBq/microg, respectively. Tumor uptake of the (111)In-, (86)Y- and (68)Ga-labeled 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 of the kidneys. Melanoma tumors were imaged with all three radiolabeled peptides 2 h postinjection. MC1-R-specific uptake was confirmed by competitive receptor blocking studies.
Conclusions: Melanoma tumor uptake and imaging was exhibited by the (111)In-, (86)Y- and (68)Ga-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 (111)In, (86)Y and (68)Ga labeling.