論文

査読有り
2002年5月

Synthesis and evaluation of 3-(4-chlorobenzyl)-8-[C-11]methoxy-1,2,3,4-tetrahydrochromeno[3,4-c]pyridin-5-one: a PET tracer for imaging sigma(1) receptors

NUCLEAR MEDICINE AND BIOLOGY
  • MR Zhang
  • ,
  • T Haradahira
  • ,
  • J Maeda
  • ,
  • T Okauchi
  • ,
  • K Kawabe
  • ,
  • T Kida
  • ,
  • S Obayashi
  • ,
  • K Suzuki
  • ,
  • T Suhara

29
4
開始ページ
469
終了ページ
476
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/S0969-8051(02)00293-7
出版者・発行元
ELSEVIER SCIENCE INC

3 - (4-Chlorobenzyl)-8-methoxy- 1,2,3,4-tetrahydrochromeno [3,4-c]pyridin-5-one (1), a putative dopamine D-4 receptor antagonist (k(i) = 8.7 nM), was labeled by positron-emitter (C-11) and its pharmacological evaluation was carried out with in vitro quantitative autoradiography and positron emission tomography (PET). C-11-Methylation of a corresponding desmethyl precursor (2) with [C-11]CH3I gave [C-11]1 with greater than or equal to98% of radiochemical purity after HPLC purification and 67-90 GBq/mumol of specific activity at the end of synthesis. The in vitro autoradiography using rat brain sections demonstrated that [C-11] I shows no specific binding to the D-4 receptors, but a high specific binding to sigma, receptors (IC50 = 105 nM). In the PET study with monkey brain, [C-11] 1 was highly taken up by the brain and trapped in the brain for at least 90 min. The distribution pattern of radioactivity in the brain was striatum > thalamus > frontal cortex > cerebellum, which was same as the result of in vitro autoradiography. Pre-treatment with non-radioactive 1 (1 mg/kg) produced a significant reduction of radioactivity in all the regions including the cerebellum. Pre-treatment with (+)pentazocine (I mg/kg), a selective sigma(1) receptor agonist, also reduced the radioactivity in the same regions to a similar extent. These results indicate that [C-11] 1 may have some specific binding to the sigma, receptors, which is consistent with the result of in vitro autoradiography. (C) 2002 Elsevier Science Inc. All rights reserved.

Web of Science ® 被引用回数 : 25

リンク情報
DOI
https://doi.org/10.1016/S0969-8051(02)00293-7
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/12031882
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000175794400011&DestApp=WOS_CPL
ID情報
  • DOI : 10.1016/S0969-8051(02)00293-7
  • ISSN : 0969-8051
  • PubMed ID : 12031882
  • Web of Science ID : WOS:000175794400011

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