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 Esterlis, Irina
A1 Hannestad, Jonas O.
A1 Bois, Frederic
A1 Sewell, R. Andrew
A1 Tyndale, Rachel F.
A1 Seibyl, John P.
A1 Picciotto, Marina R.
A1 Laruelle, Marc
A1 Carson, Richard E.
A1 Cosgrove, Kelly P.
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.