title: Imaging changes in synaptic acetylcholine availability in living human subjects.
abstract: In vivo estimation of β(2)-nicotinic acetylcholine receptor availability with molecular neuroimaging is complicated by competition between the endogenous neurotransmitter acetylcholine and the radioligand (123)I-3-[2(S)-2-azetidinylmethoxy]pyridine ((123)I-5-IA). We examined whether binding of (123)I-5-IA is sensitive to increases in extracellular levels of acetylcholine in humans, as suggested in nonhuman primates.
  
  
  METHODS
  Six healthy subjects (31 ± 4 y) participated in a (123)I-5-IA SPECT study. After baseline scans, physostigmine (1-1.5 mg) was administered intravenously over 60 min, and 9 additional scans were obtained.
  
  
  RESULTS
  We observed a significant reduction in the total volume of distribution after physostigmine administration (29% ± 17% in the cortex, 19% ± 15% in the thalamus, 19% ± 15% in the striatum, and 36% ± 30% in the cerebellum; P < 0.05). This reduction reflected a combination of a region-specific 7%-16% decrease in tissue concentration of tracer and a 9% increase in plasma parent concentration.
  
  
  CONCLUSIONS
  These data suggest that increases in acetylcholine compete with (123)I-5-IA for binding to β(2)-nicotinic acetylcholine receptor. Additional validation of this paradigm is warranted, but it may be used to interrogate changes in extracellular acetylcholine.
authors.affiliation: Department of Psychiatry, Yale University, New Haven, Connecticut, USA. irina.esterlis@yale.edu
authors.forename: Irina
authors.initials: I
authors.lastname: Esterlis
authors.forename: Jonas O
authors.initials: JO
authors.lastname: Hannestad
authors.forename: Frederic
authors.initials: F
authors.lastname: Bois
authors.forename: R Andrew
authors.initials: RA
authors.lastname: Sewell
authors.forename: Rachel F
authors.initials: RF
authors.lastname: Tyndale
authors.forename: John P
authors.initials: JP
authors.lastname: Seibyl
authors.forename: Marina R
authors.initials: MR
authors.lastname: Picciotto
authors.forename: Marc
authors.initials: M
authors.lastname: Laruelle
authors.forename: Richard E
authors.initials: RE
authors.lastname: Carson
authors.forename: Kelly P
authors.initials: KP
authors.lastname: Cosgrove
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000328:Adult; D001384:Azetidines / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000000981:diagnostic imaging; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D010830:Physostigmine / Q000494:pharmacology; D011725:Pyridines / Q000378:metabolism; D013569:Synapses / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism*; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: C426745:5-iodo-3-(2-azetidinylmethoxy)pyridine; D001384:Azetidines; D011725:Pyridines; D010830:Physostigmine; D000109:Acetylcholine