Esterlis_2013_J.Nucl.Med_54_78

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.