Synthesis of carbon-11 labeled biaryl 1,2,3,4-tetrahydroisoquinoline derivatives and conformationally flexible analogues as new potential PET glioma tumor imaging agents

Carbon-11 labeled biaryl 1,2,3,4-tetrahydroisoquinoline derivatives and conformationally flexible analogues, 2-(2-(biphenyl-4-yl)ethyl)-6-[11C]methoxy-7-methoxy-1,2,3,4-tetrahydroisoquinoline ([11C]3); 1-(biphenyl-4-yl)methyl-6,7-dimethoxy-2-[11C]methyl-1,2,3,4-tetrahydroisoquinoline (N-[11C]7) and 1-(biphenyl-4-yl)methyl-6-[11C]methoxy-7-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline (O-[11C]7); and 2-(biphenyl-4-yl)-N-(3,4-dimethoxy-phenethyl)-N-[11C]methyl-ethanamine (N-[11C]10) and 2-(biphenyl-4-yl)-N-(3-methoxy-4-[11C]methoxy-phenethyl)-N-methyl-ethanamine (O-[11C]10), have been synthesized as new potential positron emission tomography (PET) glioma tumor imaging agents, either by O-[11C]methylation or by N-[11C]methylation of the appropriate precursors using [11C]CH3OTf and isolated either by a simplified solid-phase extraction (SPE) purification procedure or by HPLC method in 30–55% radiochemical yields decay corrected to EOB, 15–25 min overall synthesis time, and 4.0–6.0 Ci/μmol specific activity at EOB.