Development of high-specific-activity 68Ga-labeled DOTA-rhenium-cyclized α-MSH peptide analog to target MC1 receptors overexpressed by melanoma tumors

IntroductionA previous report on 68Ga-1,4,7,10-tetraazacyclodedecane-N,N′,N″,N′″-tetraacetic acid (DOTA)-Re(Arg11)CCMSH was shown to indicate the imaging agent's potency for early detection of metastatic melanoma. However, the main limiting factor to developing high-specific-activity 68Ga-DOTA-Re(Arg11)CCMSH is the short half-life of 68Ga, which precludes further purification of the agent. To circumvent this problem, we incorporated the microwave technique to rapidly radiolabel the peptide with 68Ga, thereby allowing enough time to include high-performance liquid chromatography (HPLC) purification in the overall procedure.MethodsDOTA-Re(Arg11)CCMSH was radiolabeled with 68Ga in <1 min using a circular-cavity microwave apparatus. Reverse-phase HPLC purification was accomplished in less than 20 min. 68Ga-DOTA-Re(Arg11)CCMSH was then administered on B16/F1 murine melanoma-bearing C57 mice to study its biodistribution and positron emission tomography (PET) imaging capability.ResultsThe production of high-specific-activity 68Ga-DOTA-Re(Arg11)CCMSH resulted in an improved tumor uptake [6.93±1.11%ID/g at 30 min postinjection (p.i.) and 6.27±1.60%ID/g at 1 h p.i.] and tumor retention (5.85±1.32%ID/g at 4 h p.i.). Receptor-mediated tumor uptake was verified by blocking studies. Furthermore, high-resolution PET images of the tumor were obtained, owing to high tumor-to-nontarget organ ratios at an early time point (i.e., at 1 h biodistribution: tumor/blood, 14.3; tumor/muscle, 89.6; tumor/skin, 12.3) and fast clearance of the labeled peptide from kidney and other healthy tissues.ConclusionHigh-specific-activity 68Ga-DOTA-Re(Arg11)CCMSH may have a potential role in the early diagnosis of metastasized melanoma.