In vivo estimation of beta(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. CONCLUSION: These data suggest that increases in acetylcholine compete with (123)I-5-IA for binding to beta(2)-nicotinic acetylcholine receptor. Additional validation of this paradigm is warranted, but it may be used to interrogate changes in extracellular acetylcholine.
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Esterlis I, Hannestad JO, Bois F, Sewell RA, Tyndale RF, Seibyl JP, Picciotto MR, Laruelle M, Carson RE, Cosgrove KP (2013) Imaging changes in synaptic acetylcholine availability in living human subjects J Nucl Med54: 78-82
Esterlis I, Hannestad JO, Bois F, Sewell RA, Tyndale RF, Seibyl JP, Picciotto MR, Laruelle M, Carson RE, Cosgrove KP (2013) J Nucl Med54: 78-82
