[11C](+)McN5652 as a radiotracer for imaging serotonin uptake sites with pet

Makiko Suehiro, Ursula Scheffel, Hayden T. Ravert, Robert F. Dannals, Henry N. Wagner

Research output: Contribution to journalArticle

Abstract

The in vivo behavior of the stereoisomers of [11C]McN5652, a highly potent serotonin (5-HT) uptake blocker, was determined to evaluate their utility as radiotracers for imaging 5-HT uptake sites by positron emission tomography (PET). After intravenous injection into mice, [11C](+)McN5652 showed markedly higher uptake and longer retention in regions with high density of 5-HT uptake sites than the [11C]-labeled racemic mixture, while [11C](-)McN5652 washed out rapidly. With the [11C](+)-enantiomer, the ratio between hypothalamus and cerebellum reached 6 at 90 minutes. The binding of [11C](+)McN5652 was inhibited by 45-73% by pre-injection of 5 mg/kg of paroxetine, a selective 5-HT uptake blocker, in all regions examined except cerebellum where no significant effect of the drug was observed. [11C](-)McN5652 showed no specific binding in any of the regions. The [11C]-labeled cis isomer, [11C]McN5655, revealed surprisingly low brain penetration and showed no significantly higher uptake in regions of interest than cerebellum. These results suggest that [11C](+)McN5652 is a promising candidate as a PET radiotracer for studying 5-HT uptake sites in vivo.

Original languageEnglish (US)
Pages (from-to)883-892
Number of pages10
JournalLife Sciences
Volume53
Issue number11
DOIs
StatePublished - 1993

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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