Synthesis and initial PET imaging of new potential dopaimine D3 receptor radioligands (E)-4,3,2-[11C]methoxy-N-4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl-cinnamoylamides

D-3 receptor radioligands (E)-4,3,2-[C-11]methoxy-N-4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl-cinnamoylamides (4-[C-11]MMC, [C-11]1a; 3-[C-11]MMC, [C-11]1b; and 2-[C-11]MMC, [C-11]1c) were synthesized for evaluation as novel potential positron emission tomography (PET) imaging agents for brain D-3 receptors. The new tracers 4,3,2-[C-11]MMCs were prepared by 0-[C-11]methylation of corresponding precursors (E)-4,3,2-hydroxy-N-4-(4-(2-methoxyphenyl)piperazin-l-yl)butyl-cinnamoylamides (4,3,2-HMCs) using [C-11]methyl triflate and isolated by the solid-phase extraction (SPE) purification procedure with 40-65% radiochemical ' Ids, decay corrected to end of bombardment (EOB), and a synthesis time of 15-20 min. The PET dynamic studies of the tracers [C-11]1a-c in rats were performed using an animal PET scanner, IndyPET-11, developed in our laboratory. The results show that the brain uptake sequence was 4-[C-11]MMC > 3-[C-11]MNIC > 2-[C-11]MMC, which is consistent with their in vitro biological properties. The initial PET blocking studies of the tracers 4,3,2-[C-11]MMCs with corresponding pretreatment drugs (E)-4,3,2-methoxy-N-4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl-cinnamoylamides (4,3,2-MMCs, 1a-c) bad no effect on 4,3,2-[C-11]MMCs-PET rat brain imaging. These results suggest that the localization of 4,3,2-[C-11]MMCs in rat brain is mediated by nonspecific processes, and the visualization of 4,3,2-[C-11]MMCs-PET in rat brain is related to nonspecific binding. (c) 2005 Elsevier Ltd. All rights reserved.