RT Journal Article SR Electronic T1 Imaging Changes in Synaptic Acetylcholine Availability in Living Human Subjects JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 78 OP 82 DO 10.2967/jnumed.112.111922 VO 54 IS 1 A1 Irina Esterlis A1 Jonas O. Hannestad A1 Frederic Bois A1 R. Andrew Sewell A1 Rachel F. Tyndale A1 John P. Seibyl A1 Marina R. Picciotto A1 Marc Laruelle A1 Richard E. Carson A1 Kelly P. Cosgrove YR 2013 UL http://jnm.snmjournals.org/content/54/1/78.abstract AB In vivo estimation of β2-nicotinic acetylcholine receptor availability with molecular neuroimaging is complicated by competition between the endogenous neurotransmitter acetylcholine and the radioligand 123I-3-[2(S)-2-azetidinylmethoxy]pyridine (123I-5-IA). We examined whether binding of 123I-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 123I-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. Conclusion: These data suggest that increases in acetylcholine compete with 123I-5-IA for binding to β2-nicotinic acetylcholine receptor. Additional validation of this paradigm is warranted, but it may be used to interrogate changes in extracellular acetylcholine.