Synthesis, in vitro and in vivo pharmacology of a C-11 labeled analog of CP-101,606, (±)threo-1-(4-hydroxyphenyl)-2-[4-hydroxy-4- (p-[11C]methoxyphenyl)piperidino]-1-propanol, as a PET tracer for NR2B subunit-containing NMDA receptors

Terushi Haradahira, Jun Maeda, Takashi Okauchi, Ming Rong Zhang, Junko Hojo, Takayo Kida, Takuya Arai, Fumihiko Yamamoto, Shigeki Sasaki, Minoru Maeda, Kazutoshi Suzuki, Tetsuya Suhara

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A carbon-11 labeled methoxyl analog of CP-101,606, (±)threo-1-(4-hydroxyphenyl)-2-[4-hydroxy-4-(p-[11C] methoxyphenyl)piperidino]-1-propanol [(±)[11C]1], was synthesized as a new subtype-selective PET radioligand for NMDA receptors. The in vitro binding studies using rat brain slices demonstrated that (±)[11C]1 shows an extremely high-specific binding to the NR2B subunit of NMDA receptors. In contrast to the in vitro binding, the in vivo binding to mouse and monkey brains showed no apparent specific localization of the radioactivity in any of the brain regions. Metabolism and physicochemical properties such as the lipophilicity of (±)[11C]1 seemed unlikely to affect the in vivo (±)[11C]1 binding. Among the various endogenous ligands acting at the NMDA receptors, polyamines (spermine and spermidine) and divalent cations (Mg2+, Zn2+, and Ca2+) strongly inhibited the in vitro (±)[11C]1 binding. Thus, the present studies point to the possibility that the polyamines and cations behave as endogenous inhibitors for (±)[11C]1 binding, leading to the loss of the specific binding in vivo.

Original languageEnglish
Pages (from-to)517-525
Number of pages9
JournalNuclear Medicine and Biology
Issue number5
Publication statusPublished - Jul 2 2002


All Science Journal Classification (ASJC) codes

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

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