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

Abstract 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/μg, 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.