Imaging changes in synaptic acetylcholine availability in living human subjects.
Imaging changes in synaptic acetylcholine availability in living human subjects.
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DOI：
10.2967/jnumed.112.111922
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发表时间：
2013-01
期刊：
影响因子：
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通讯作者：
Cosgrove KP
中科院分区：
文献类型：
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作者：
Esterlis I;Hannestad JO;Bois F;Sewell RA;Tyndale RF;Seibyl JP;Picciotto MR;Laruelle M;Carson RE;Cosgrove KP
内源性神经递质ACh和放射性配体[123 I]5-IA-85380（[123 I]5-IA）之间的竞争使采用分子神经成像技术对β 2-烟碱乙酰胆碱受体（β2*-nAChR）可用性的体内评估变得复杂。我们研究了[123 I]5-IA的结合是否对人类细胞外ACh水平的增加敏感，如在非人类灵长类动物中所建议的那样。6例健康受试者（31± 4岁）参加了一项[123 I]5-IA SPECT研究。基线扫描后，在60分钟内静脉注射毒扁豆碱（1- 1.5 mg），并收集额外的扫描（8- 14 h）。我们观察到毒扁豆碱后VT/fp（总分布容积）显著降低（皮质29±17%，丘脑19 ± 15%，纹状体19 ±15%，小脑36±30%; p<0.05）。这反映了示踪剂组织浓度的区域特异性降低7-16%和血浆母体浓度增加9%的组合。这些数据表明，ACh的增加与[123 I]5-IA竞争结合β2*-nAChR。这一范例的额外验证是必要的，但它可以用来询问细胞外乙酰胆碱的变化。
In vivo estimation of beta2-nicotinic acetylcholine receptor (β2*-nAChR) availability with molecular neuroimaging is complicated by competition between the endogenous neurotransmitter ACh and the radioligand [123I]5-IA-85380 ([123I]5-IA). We examined whether binding of [123I]5-IA is sensitive to increases in extracellular levels of ACh in humans, as suggested in non-human primates. Six healthy subjects (31±4yrs) participated in one [123I]5-IA SPECT study. After baseline scans, physostigmine (1–1.5mg) was administered IV over 60 min, and additional scans were collected (8–14h). We observed a significant reduction in VT/fp (total volume of distribution) after physostigmine (29±17% cortex, 19±15% thalamus, 19±15% striatum, and 36±30% cerebellum; p<.05). This reflected a combination of a region-specific 7–16% decrease in tissue concentration of tracer and 9% increase in plasma parent concentration. These data suggest that increases in ACh compete with [123I]5-IA for binding to β2*-nAChRs. Additional validation of this paradigm is warranted, but it may be used to interrogate changes in extracellular ACh.