Innis R, Zoghbi S, Johnson E, Woods S, al-Tikriti M, Baldwin R, Seibyl J, Malison R, Zubal G, Charney D
West Haven VA Medical Center, CT.
Eur J Pharmacol. 1991 Feb 7;193(2):249-52. doi: 10.1016/0014-2999(91)90043-p.
We have used SPECT (single photon emission computed tomography) imaging in non-human primates to examine the time course and pharmacological specificity of 123I-labeled Ro 16-0154 as an in vivo probe of the benzodiazepine receptor. Maximal brain uptake was reached approximately 70 min post i.v. administration of the radioligand and represented approximately 10% of the injected dose. The regional distribution of radioactive densities was consistent with the known distribution of benzodiazepine receptors in primate brain, with highest uptake localized over the occipital area. Washout of radioactivity was relatively slow with a rate of 3% per hour after the time of peak radioactivity. Injection of the benzodiazepine antagonist Ro 15-1788 (0.2-0.3 mg/kg i.v.) caused a rapid decrease of more than 90% of radioactivity from brain. In summary, [123I]Ro 16-0154 is a promising in vivo SPECT radioligand for the benzodiazepine receptor, with high brain uptake, a stable period of peak radioactivity, appropriate regional distribution, and ability to be displaced by other benzodiazepine receptor agents.
我们已在非人类灵长类动物中使用单光子发射计算机断层扫描（SPECT）成像技术，以研究作为苯二氮䓬受体体内探针的123I标记的Ro 16-0154的时间进程和药理学特异性。静脉注射放射性配体后约70分钟达到最大脑摄取量，约占注射剂量的10%。放射性密度的区域分布与灵长类动物脑中已知的苯二氮䓬受体分布一致，最高摄取位于枕叶区域。放射性物质的清除相对较慢，在放射性达到峰值后每小时清除率为3%。静脉注射苯二氮䓬拮抗剂Ro 15-1788（0.2-0.3毫克/千克）导致脑内放射性迅速降低超过90%。总之，[123I]Ro 16-0154是一种很有前景的用于苯二氮䓬受体的体内SPECT放射性配体，具有高脑摄取、放射性峰值稳定期、合适的区域分布以及能被其他苯二氮䓬受体药物取代的能力。
