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

作者：Cantorias Melchor V; Figueroa Said D; Quinn Thomas P; Lever John R; Hoffman Timothy J; Watkinson Lisa D; Carmack Terry L; Cutler Cathy S^*

来源：Nuclear Medicine and Biology, 2009, 36(5): 505-513.

DOI：10.1016/j.nucmedbio.2009.01.017

• alpha-Melanocyte-stimulating hormone
• Ga-68
• PET
• Microwave labeling
• Specific activity
• HPLC purification

Introduction: A previous report on Ga-68-1,4,7,10-tetraazacyclocledecatic-N,N',N '',N'''-tetraacetic acid (DOTA)-Re(Arg(11))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 Ga-68-DOTA-Re(Arg(11))CCMSH is the short half-life of Ga-68, which precludes further purification of the agent. To circumvent this problem, we incorporated the microwave technique to rapidly radiolabel the peptide with Ga-68, thereby allowing enough time to include high-performance liquid chromatography (HPLC) purification in the overall procedure.
Methods: DOTA-Re(Arg(11))CCMSH was radiolabeled with Ga-68 in <1 min using a circular-cavity microwave apparatus. Reverse-phase HPLC purification was accomplished in less than 20 min. Ga-68-DOTA-Re(Arg(11))CCMSH was then administered on B16/FI murine melanoma-bearing C57 mice to study its biodistribution and positron emission tomography (PET) imaging capability.
Results: The production of high-specific-activity Ga-68-DOTA-Re(Arg(11))CCMSH resulted in ail improved turnor 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 Ga-68-DOTA-Re(Arg(11))CCMSH may have a potential role in the early diagnosis of metastasized melanoma.

• 出版日期2009-7