Synthesis of carbon-11-labeled 4-aryl-4H-chromens as new PET agents for imaging of apoptosis in cancer

Carbon-11-labeled 4-aryl-4H-chromenes, 2-amino-7-(dimethylamino)-4-(3-C-11]methoxy-5-methoxypheny1)-4H-chromene-3-carbonitrile ([C-11]6a), 2-amino-4-(3-bromo-4-[C-11]methoxy-5-methoxyphenyl)-7-(dimethylamino)-4H-chromene-3-carbonitrile ([C-11]6c), 2-amino-4-(3-C-11]methoxy-5methoxypheny1)-4,7-dihydropyrano[2,3-elindole-3-carbonitrile([C-11]6d), 2-amino-4-(3-bromo-4-C-11]methoxy-5-methoxyphenyl)-4,7-dihydropyrano[2,3-elindole-3-carbonitrile ([C-11)6f), 2-amino-4-(3-[C-11]methoxy-5-methoxypheny1)-4,9-dihydropyrano[3,2-glindole-3-carbonitrile ([(11)C16g), 2-amino-4(3-bromo-4-[C-11]methoxy-5-methoxyphenyl)-4,9-dihydropyrano[3,2-glindole-3-carbonitrile ([C-11]6i), 2-amino-4-(3-[C-11]methoxy-5-methoxyphenyl)-7-methyl-4,7-dihydroPyrano[2,3-elindole-3-carbonitrile ([C-11]6j) and 2-amino-4-(3-bromo-4-[C-11]methoxy-5-methoxyphenyl)-7-methyl-4,7-dihydroPyrano[2,3-e]indole-3-carbonitrile ([C-11]6l), were prepared by 0-(11C]methylation of their corresponding precursors using [C-11]CH3OTf under basic conditions and isolated by a simplified solid-phase extraction (SPE) method in 30-50% radiochemical yields based on [C-11]CO2 and decay corrected to end of bombardment (EOB). The overall synthesis time from EOB was 15-20 min, the radiochemical purity was >99%, and the specific activity at end of synthesis (EOS) was 111-185 GBq/mu mol. (C) 2009 Elsevier Ltd. All rights reserved.