N-METHYLQUIPAZINE - C-11 LABELING OF THE 5-HT3 AGONIST AND IN-VIVO EVALUATION OF ITS BIODISTRIBUTION USING PET

N-Methylquipazine ((2-[1-(4-methyl)-piperazinyl)quinoline)) was labell ed with carbon-11 by reacting [C-11]methyl iodide with the nor-compoun d, quipazine. Radiochemical conversions were 79 +/- 7%, based on the a lkylating agent. The total synthesis time including purification was 4 0 to 45 min, N-[Methyl-C-11]methylquipazine thus synthesized was >99% radiochemically pure, and the specific activity ranged between 12-37 G Bq/mu mol. Dynamic imaging with PET was used to examine in vivo its di stribution in rat and monkey, In rat the organ uptake at intermediate times was: liver > heart > whole brain greater than or equal to lung > extracerebral tissue. Brain uptake and wash-out were rapid: A maximum was reached in 2 to 3 min with subsequent decrease to approximate to 50% the peak value by 13 min. In monkey the tracer uptake was heteroge neous and high in regions known to contain 5-HT3 receptors but also in regions devoid of these receptors. Tissue kinetics were similar for a ll regions (initial rapid accumulation with t(max) less than or equal to 7 min, followed by slow decrease with all regions approaching the l evel of the cerebellum at 30 to 35 min). Pretreating with quipazine si gnificantly decreased only the ratio of uptake in the medulla oblongat a compared to the cerebellum. Although the nonspecificity of its bindi ng limits the usefulness of N-[methyl-C-11]methylquipazine, both its k inetic behavior and the blocking results indicate that a more selectiv e arylpiperazine might prove to be a more attractive tracer for PET st udies of 5-HT3 receptors. (C) 1997 Elsevier Science Inc.