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-[11C]methoxy-5-methoxyphenyl)-4H-chromene-3-carbonitrile ([11C]6a), 2-amino-4-(3-bromo-4-[11C]methoxy-5-methoxyphenyl)-7-(dimethylamino)-4H-chromene-3-carbonitrile ([11C]6c), 2-amino-4-(3-[11C]methoxy-5-methoxyphenyl)-4,7-dihydropyrano[2,3-e]indole-3-carbonitrile ([11C]6d), 2-amino-4-(3-bromo-4-[11C]methoxy-5-methoxyphenyl)-4,7-dihydropyrano[2,3-e]indole-3-carbonitrile ([11C]6f), 2-amino-4-(3-[11C]methoxy-5-methoxyphenyl)-4,9-dihydropyrano[3,2-g]indole-3-carbonitrile ([11C]6g), 2-amino-4-(3-bromo-4-[11C]methoxy-5-methoxyphenyl)-4,9-dihydropyrano[3,2-g]indole-3-carbonitrile ([11C]6i), 2-amino-4-(3-[11C]methoxy-5-methoxyphenyl)-7-methyl-4,7-dihydropyrano[2,3-e]indole-3-carbonitrile ([11C]6j) and 2-amino-4-(3-bromo-4-[11C]methoxy-5-methoxyphenyl)-7-methyl-4,7-dihydropyrano[2,3-e]indole-3-carbonitrile ([11C]6l), were prepared by O-[11C]methylation of their corresponding precursors using [11C]CH3OTf under basic conditions and isolated by a simplified solid-phase extraction (SPE) method in 30–50% radiochemical yields based on [11C]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/μmol.