Breast cancer resistance protein (ABCG2) is an attractive target for the development of therapeutic agents for use in breast cancer treatment, and diagnostic agents for use in breast cancer detection by the biomedical imaging technique positron emission tomography (PET). Quinoline-2-carboxamido and quinoline-3-carboxamido are two potent and selective inhibitors of ABCG2. This study was designed to develop carbon-11-labeled quinoline-2-carboxamido and quinoline-3-carboxamido as new PET agents for imaging of ABCG2. Unlabeled reference standards, methyl 4-((4-(2-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-2-yl)ethyl)phenyl)aminocarbonyl)-2-(quinoline-2-carbonylamino)benzoate and methyl 4-((4-(2-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-2-yl)ethyl)phenyl)aminocarbonyl)-2-(quinoline-3-carbonylamino)benzoate, and their acid precursors, 4-((4-(2-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-2-yl)ethyl)phenyl)aminocarbonyl)-2-(quinoline-2-carbonylamino)benzoic acid and 4-((4-(2-(6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline-2-yl)ethyl)phenyl)aminocarbonyl)-2-(quinoline-3-carbonylamino)benzoic acid, were synthesized from the starting material 2-(3,4-dimethoxyphenyl)ethylamine in multiple steps with moderate to excellent yields. The target tracers, [11C]methyl 4-((4-(2-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-2-yl)ethyl)phenyl)aminocarbonyl)-2-(quinoline-2-carbonylamino)benzoate and [11C]methyl 4-((4-(2-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-2-yl)ethyl)phenyl)aminocarbonyl)-2-(quinoline-3-carbonylamino)benzoate, were prepared from their corresponding acid precursors with [11C]methyl triflate ([11C]CH3OTf) under basic conditions through O-[11C]methylation and isolated by a simplified solid-phase extraction (SPE) method in 50-60% radiochemical yields and 111-185 GBq/�mol specific activity at the end of synthesis (EOS).

Synthesis of carbon-11-labeled quinoline-2-carboxamido and quinoline-3-carboxamido as new PET agents for imaging of breast cancer resistance protein

239th National Meeting (2010)

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