Synthesis and evaluation of 1-{1-[5-(2′-[18F]Fluoroethyl)-2-thienyl]-cyclohexyl}piperidine as a potential in vivo radioligand for the NMDA receptor-Channel complex

Kazuhiro Orita, Shigeki Sasaki, Minoru Maeda, Atsushi Hashimoto, Toru Nishikawa, Tomoko Yugami, Kohei Umezu

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Abstract

1-{1-[5-(2′-[18F]Fluoroethyl)-2-thienyl]cyclohexyl}piperidine (18FE-TCP) was prepared as a fluorine-substituted analogue of the potent NMDA receptor channel blocker, 1-[1-(2-thienyl)cyclohexyl]piperidine (TCP), by the mesylate displacement with [18F]fluoride ion with isolated radiochemical yields of 6-12%, and the synthesis time including a two step HPLC purification was 120 min. The regional distribution in rat brain after i.v. injection of 18FE-TCP was heterogeneous and similar to the known distribution of phencyclidine recognition sites, with hippocampus-cerebellum, striatum-cerebellum and cerebral cortex-cerebellum concentration ratios of 2.08, 1.7 and 1.54, respectively, 15 min post-injection. Furthermore, this localized regional cerebral distribution was blocked by co-injection with the unlabelled FE-TCP or pretreatment with cis-2-hydroxymethyl-r-1-(N-piperidyl)-1-(2-thienyl)cyclohexane, with the greatest reductions seen in the hippocampus followed by the striatum and cerebral cortex. However, relatively low receptor binding affinity and high non-specific binding due to its high lipophilicity suggest that 18FE-TCP may not be a suitable radioligand for in vivo PET investigations of the NMDA receptor-channel complex.

Original languageEnglish
Pages (from-to)865-873
Number of pages9
JournalNuclear Medicine and Biology
Volume20
Issue number7
DOIs
Publication statusPublished - Oct 1993

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N-Methyl-D-Aspartate Receptors
Cerebellum
tenocyclidine
Cerebral Cortex
Injections
Hippocampus
Phencyclidine
Mesylates
Fluorine
Fluorides
High Pressure Liquid Chromatography
Ions
Brain
1-(1-(5-(2'-fluoroethyl)-2-thienyl)-cyclohexyl)piperidine

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

Synthesis and evaluation of 1-{1-[5-(2′-[18F]Fluoroethyl)-2-thienyl]-cyclohexyl}piperidine as a potential in vivo radioligand for the NMDA receptor-Channel complex. / Orita, Kazuhiro; Sasaki, Shigeki; Maeda, Minoru; Hashimoto, Atsushi; Nishikawa, Toru; Yugami, Tomoko; Umezu, Kohei.

In: Nuclear Medicine and Biology, Vol. 20, No. 7, 10.1993, p. 865-873.

Research output: Contribution to journalArticle

Orita, Kazuhiro ; Sasaki, Shigeki ; Maeda, Minoru ; Hashimoto, Atsushi ; Nishikawa, Toru ; Yugami, Tomoko ; Umezu, Kohei. / Synthesis and evaluation of 1-{1-[5-(2′-[18F]Fluoroethyl)-2-thienyl]-cyclohexyl}piperidine as a potential in vivo radioligand for the NMDA receptor-Channel complex. In: Nuclear Medicine and Biology. 1993 ; Vol. 20, No. 7. pp. 865-873.
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