期刊
BIOORGANIC & MEDICINAL CHEMISTRY
卷 19, 期 17, 页码 5255-5259出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2011.06.090
关键词
PET; Brain; Carbon-11; Radiotracer; Serotonin
The serotonin receptor 6 (5-HT6) is implicated in the pathophysiology of cognitive diseases, schizophrenia, anxiety and obesity and in vivo studies of this receptor would be of value for studying the pathophysiology of these disorders. Therefore, N-[3,5-dichloro-2-(methoxy) phenyl]-4-(methoxy)-3-(1-piperazinyl) benzenesulfonamide (SB399885), a selective and high affinity (pK(i) = 9.11) 5-HT6 antagonist, has been radiolabeled with carbon-11 by O-methylation of the corresponding desmethyl analogue with [C-11]MeOTf in order to determine the suitability of [C-11]SB399885 to quantify 5-HT6R in living brain using PET. Desmethyl-SB399885 was prepared, starting from 1-(2-methoxyphenyl) piperazine hydrochloride, in excellent yield. The yield obtained for radiolabeling of [C-11]SB399885 was 30 +/- 5% (EOS) and the total synthesis time was 30 min at EOB. PET studies with [C-11]SB399885 in baboon showed fast uptake followed by rapid clearance in the brain. Highest uptake of radioactivity of [C-11]SB399885 in baboon brain were found in temporal cortex, parahippocampal gyrus, pareital cortex, amygdala, and hippocampus. Poor brain entry and inconsistent brain uptake of [C-11]SB399885 compared to known 5-HT6R distribution limits its usefulness for the in vivo quantification of 5-HT6R with PET. (C) 2011 Elsevier Ltd. All rights reserved.
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