title: 2-[18F]F-A-85380: PET imaging of brain nicotinic acetylcholine receptors and whole body distribution in humans.
abstract: Noninvasive imaging of nicotinic acetylcholine receptors (nAChRs) in the human brain in vivo is critical for elucidating the role of these receptors in normal brain function and in the pathogenesis of brain disorders. Here we report the first in vivo visualization of human brain areas containing nAChRs by using PET and 2-[18F]fluoro-3-(2(S)azetidinylmethoxy)pyridine (2-[18F]FA). We acquired scans from six healthy non-smoking volunteers after i.v. bolus administration of 2-[18F]FA (1.6 MBq/kg or 0.043 +/- 0.002 mCi/kg). This dose was sufficient for visualizing nAChRs in the thalamus up to 5 h after injection. There were no adverse effects associated with administration of no-carrier-added 2-[18F]FA (1.3-10 pmol/kg). Consistent with the distribution of nAChRs in human brain, accumulated radioactivity was greatest in thalamus, intermediate in the midbrain, pons, cerebellum, and cortex; and least in white matter. As approximately 90% of the injected radioactivity was eliminated via the urine (biological half-life ca. 4 h), the urinary bladder wall received the highest radiation dose. The estimate of radiation dose equivalent to the urinary bladder wall (ca. 180 +/- 30 mSv/MBq or 0.7 rem/mCi with a 2.4 h void interval) suggests that multiple studies could be performed in a single subject. The results predict that quantitative PET imaging of nAChRs in human brain with 2-[18F]FA is feasible.
authors.affiliation: NIDA Intramural Research Program; Baltimore, Maryland 21224, USA. akimes@intra.nida.nih.gov
authors.forename: Alane S
authors.initials: AS
authors.lastname: Kimes
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Horti
authors.forename: Edythe D
authors.initials: ED
authors.lastname: London
authors.forename: Svetlana I
authors.initials: SI
authors.lastname: Chefer
authors.forename: Carlo
authors.initials: C
authors.lastname: Contoreggi
authors.forename: Monique
authors.initials: M
authors.lastname: Ernst
authors.forename: Phyllis
authors.initials: P
authors.lastname: Friello
authors.forename: Andrei O
authors.initials: AO
authors.lastname: Koren
authors.forename: Varughese
authors.initials: V
authors.lastname: Kurian
authors.forename: John A
authors.initials: JA
authors.lastname: Matochik
authors.forename: Olga
authors.initials: O
authors.lastname: Pavlova
authors.forename: D Bruce
authors.initials: DB
authors.lastname: Vaupel
authors.forename: Alexey G
authors.initials: AG
authors.lastname: Mukhin
mesh_terms: D001384:Azetidines; D001921:Brain / Q000000981:diagnostic imaging*; D001923:Brain Chemistry; D005260:Female; D006801:Humans; D008024:Ligands; D011725:Pyridines / Q000009:adverse effects / Q000493:pharmacokinetics*; D011829:Radiation Dosage; D011978:Receptors, Nicotinic / Q000032:analysis*; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
chemical_list: C119803:2-fluoro-3-(2-azetidinylmethoxy)pyridine; D001384:Azetidines; D008024:Ligands; D011725:Pyridines; D011978:Receptors, Nicotinic