Imaging Changes in Synaptic Acetylcholine Availability in Living Human Subjects

• Published in: Journal of Nuclear Medicine Vol. 54; no. 1; pp. 78 - 82
• Main Authors: Esterlis, Irina, Hannestad, Jonas O., Bois, Frederic, Sewell, R. Andrew, Tyndale, Rachel F., Seibyl, John P., Picciotto, Marina R., Laruelle, Marc, Carson, Richard E., Cosgrove, Kelly P.
• Format: Journal Article
• Language: English
• Published: United States Society of Nuclear Medicine 01.01.2013
• Subjects: Acetylcholine - metabolism; Adult; Azetidines - metabolism; Brain; Brain - cytology; Brain - diagnostic imaging; Extracellular Space - drug effects; Extracellular Space - metabolism; Female; Human subjects; Humans; Male; Medical imaging; Neurotransmitters; Physostigmine - pharmacology; Pyridines - metabolism; Synapses - diagnostic imaging; Synapses - drug effects; Synapses - metabolism; T cell receptors; Tomography, Emission-Computed, Single-Photon
• ISSN: 0161-5505; 1535-5667; 2159-662X; 1535-5667
• DOI: 10.2967/jnumed.112.111922

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. 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. 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. 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.