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(Arg¹¹)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 (Arg¹¹)CCMSH and cyclized by Re incorporation to yield CHX-A″-Re(Arg¹¹)CCMSH. CHX-A″-Re(Arg¹¹)CCMSH was labeled with ¹¹¹In, ⁸⁶Y and ⁶⁸Ga, 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 ¹¹¹In-, ⁸⁶Y- and ⁶⁸Ga-labeled CHX-A″-Re(Arg¹¹)CCMSH peptides were >95%, resulting in specific activities of 4.44, 3.7 and 1.85 MBq/μg, respectively. Tumor uptake of the ¹¹¹In-, ⁸⁶Y- and ⁶⁸Ga-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 ¹¹¹In-, ⁸⁶Y- and ⁶⁸Ga-labeled Re(Arg¹¹)CCMSH peptides, although the tumor uptake was moderated by low specific activity. The facile radiolabeling properties of CHX-A″-Re(Arg¹¹)CCMSH allow it to be employed as a melanoma imaging agent with little or no purification after ¹¹¹In, ⁸⁶Y and ⁶⁸Ga labeling.