In vivo imaging of brain nicotinic acetylcholine receptors with 5-[123I]iodo-A-85380 using single photon emission computed tomography
In vivo imaging of brain nicotinic acetylcholine receptors with 5-[123I]iodo-A-85380 using single photon emission computed tomography
复制标题
DOI：
10.1016/s0024-3205(98)00514-1
复制
发表时间：
1998-11-13
期刊：
影响因子：
6.1
通讯作者：
London, ED
中科院分区：
文献类型：
--
作者：
Chefer, SI;Horti, AG;London, ED
使用单光子发射计算机断层扫描（SPECT）评价了5-[I-123]碘-A-85380（脑烟碱乙酰胆碱受体（nAChR）的新型配体）在恒河猴中的分布和动力学。在注射示踪剂后90分钟测量脑中的放射性峰值水平。放射性蓄积在丘脑中最高，在额叶皮质和基底神经节中居中，在小脑中最低。根据（丘脑-小脑）/小脑放射性比值估计的丘脑中特异性与非特异性结合（V-3”）的比值在注射后4 h达到6。在注射放射性示踪剂后2.25 h皮下注射1 mg/kg野靛碱可降低特异性结合。在金雀花碱给药后2.5 h，与金雀花碱给药时测量的水平相比，丘脑中的放射性降低了84%，额叶皮质中的放射性降低了76%，基底神经节中的放射性降低了57%，表明结合是可逆的。基于这些发现，以及其他表明动物中高亲和力、受体亚型选择性、低非特异性结合和无毒性的数据，5-[I-123]碘-A-85380似乎是人脑中nAChR SPECT成像的有希望的配体。出版社：Elsevier Science Inc.
The distribution and kinetics of 5-[I-123]iodo-A-85380, a novel ligand for brain nicotinic acetylcholine receptors (nAChRs), were evaluated in the Rhesus monkey using single photon emission computed tomography (SPECT). Peak levels of radioactivity were measured in brain at 90 min after injection of the tracer. Accumulation of radioactivity was highest in the thalamus, intermediate in the frontal cortex and basal ganglia, and lowest in the cerebellum. The ratio of specific to nonspecific binding (V-3") in the thalamus, estimated from the (thalamic - cerebellar)/cerebellar radioactivity ratio, reached a value of 6 at 4 h post-injection. Specific binding was reduced by subcutaneous injection of 1 mg/kg cytisine at 2.25 h after injection of radiotracer. At 2.5 h after cytisine administration, radioactivity in the thalamus was reduced by 84 %, in the frontal cortex, by 76%, and in the basal ganglia, by 57 % of the level measured at the time of cytisine administration, demonstrating that the binding was reversible. On the basis of these findings, together with other data indicating high affinity, receptor subtype selectivity, low nonspecific binding and lack of toxicity in animals, 5-[I-123]iodo-A-85380 appears to be a promising ligand for SPECT imaging of nAChRs in the human brain. Published by Elsevier Science Inc.