Radiosynthesis and PET imaging of [N-methyl-11C]LY257327 as a tracer for 5-HT transporters

No-carrier-added [N-methyl-11C]LY257327 was synthesized by methylation of the free base of the desmethyl precursor LY214281 with [11C]methyl iodide in anhydrous acetonitrile. Synthesis time was 52 +/- 3 min, radiochemical yield (based on [11C]methyl iodide) was 35 +/- 8%, radiochemical purity was 99 +/- 1%, and specific activity at EOB was 3900 +/- 1300 mCi/mumol. Two in vivo studies in baboon were carried out before and after pretreatment with the selective serotonin reuptake inhibitor citalopram. The first experiment showed high accumulation of radioactivity in midbrain, striatum, and thalamus, with slightly lower accumulation in the occipital and cerebellum regions. The radioactivity concentration peaked 5 min postinjection, decreasing steadily for the rest of the scanning time. The second experiment (blocked with citalopram) showed only partial inhibition of incorporation in all of the same brain regions. Although [N-methyl-11C]LY257327 displayed high brain uptake (5% of injected dose at 5 min postinjection) and localized in serotonergic areas of the brain, its target-to-nontarget ratio and its insensitivity to citalopram blocking suggest that its accumulation is dominated by nonspecific uptake. Therefore, [N-methyl-11C]LY257327 is not a useful agent for measuring serotonin reuptake sites in vivo by positron emission tomography.