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

Introduction: A 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. Methods: DOTA-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. Results: The 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. Conclusion: High-specific-activity ⁶⁸Ga-DOTA-Re(Arg¹¹)CCMSH may have a potential role in the early diagnosis of metastasized melanoma.