title: 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.
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(ND) s 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.
authors.affiliation: Division of Nuclear Medicine, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Johns Hopkins Outpatient Center, Baltimore, Maryland 21287-0807, USA. brasic@jhmi.edu
authors.forename: James Robert
authors.initials: JR
authors.lastname: Brašić
authors.forename: Nicola
authors.initials: N
authors.lastname: Cascella
authors.forename: Anil
authors.initials: A
authors.lastname: Kumar
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhou
authors.forename: John
authors.initials: J
authors.lastname: Hilton
authors.forename: Vanessa
authors.initials: V
authors.lastname: Raymont
authors.forename: Andrew
authors.initials: A
authors.lastname: Crabb
authors.forename: Maria Rita
authors.initials: MR
authors.lastname: Guevara
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Horti
authors.forename: Dean Foster
authors.initials: DF
authors.lastname: Wong
mesh_terms: D000328:Adult; D001384:Azetidines / Q000378:metabolism* / Q000493:pharmacokinetics; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D005260:Female; D005462:Fluorine Radioisotopes / Q000378:metabolism* / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000378:metabolism* / Q000493:pharmacokinetics; D011978:Receptors, Nicotinic / Q000378:metabolism; D012563:Schizophrenia, Paranoid / Q000000981:diagnostic imaging*; D012907:Smoking / Q000378:metabolism*; D055815:Young Adult
chemical_list: D001384:Azetidines; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2