Positron emission tomography experience with 2-[ 18F]fluoro-3-(2(s)-azetidinylmethoxy)pyridine (2-[ 18F]fa) in the living human brain of smokers with paranoid schizophrenia

James Robert Brašić, Nicola Cascella, Anil Kumar, Yun Zhou, John Hilton, Vanessa Raymont, Andrew Crabb, Maria Rita Guevara, Andrew G. Horti, Dean Foster Wong

Research output: Contribution to journalArticle

Abstract

Utilizing postmortem data (Breese et al. [2000] Neuropsychopharmacology 23:351-364), we hypothesized that the densities of high-affinity neuronal α4β2 nicotinic acetylcholine receptors (nAChRs) in the brain exist in a continuum from highest to lowest as follows: smokers without schizophrenia > smokers with schizophrenia > nonsmokers without schizophrenia > nonsmokers with schizophrenia. Application of the Kruskal-Wallis Test (Statacorp, 2003) to the postmortem data (Breese et al. [2000] Neuropsychopharmacology 23:351-364) confirmed the hypothesized order in the cortex and the hippocampus and attained significance in the caudate and the thalamus. Positron emission tomography (PET) was performed for 60 min at 6 h after the intravenous administration of 444 megabequerels [MBq] (12 mCi) 2-[ 18F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-[ 18F]FA), a radiotracer for high-affinity neuronal α4β2 nAChRs, as a bolus plus continuous infusion to 10 adults (seven men and three women) (six smokers including five with paranoid schizophrenia and four nonsmokers) ranging in age from 22 to 56 years (mean 40.1, standard deviation 13.6). The thalamic nondisplaceable binding potential (BP ND) was 1.32 ± 0.19 (mean ± standard deviation) for healthy control nonsmokers; 0.50 ± 0.19 for smokers with paranoid schizophrenia; and 0.51 for the single smoker without paranoid schizophrenia. The thalamic BP NDs of nonsmokers were significantly higher than those of smokers who smoked cigarettes a few hours before the scans (P = 0.0105) (StataCorp, 2003), which was likely due to occupancy of nAChRs by inhaled nicotine in smokers. Further research is needed to rule out the effects of confounding variables.

Original languageEnglish (US)
Pages (from-to)352-368
Number of pages17
JournalSynapse
Volume66
Issue number4
DOIs
StatePublished - Apr 1 2012

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Keywords

  • Kruskal-Wallis H Statistic
  • Nicotinic acetylcholine receptor
  • Rank sum tests

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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