Ma Bing, Sherman Philip S, Moskwa James E, Koeppe Robert A, Kilbourn Michael R
Division of Nuclear Medicine, Department of Radiology, University of Michigan Medical School, 3480 Kresge III Building, Ann Arbor, MI 48109, USA.
Nucl Med Biol. 2004 May;31(4):393-7. doi: 10.1016/j.nucmedbio.2003.12.009.
Administration of phenserine, an acetylcholinesterase inhibitor, raises endogenous brain acetylcholine levels and has been previously shown to reduce in vivo binding of the muscarinic cholinergic receptor antagonist [(11)C]N-methylpyrrolidinyl benzilate ([(11)C]NMPYB) in the awake rat brain. In this study, phenserine pretreatment was studied in both awake and isoflurane-anesthetized rats using the techniques of ex vivo dissection or in vivo microPET imaging. In ex vivo dissection experiments, a statistically significant 10% inhibition of [(11)C]NMPYB binding could be demonstrated in both awake and anesthetized animals after phenserine pretreatment, showing no deleterious effect of using isoflurane anesthesia. However, microPET imaging in anesthetized animals failed to successfully demonstrate inhibition of [(11)C]NMPYB binding following the identical phenserine treatment protocol. These results demonstrate that in small numbers of subjects ex vivo dissection may be a more sensitive experimental method for determining small changes of in vivo radiotracer binding in this model of neurotransmitter competition for brain receptor sites.
给予乙酰胆碱酯酶抑制剂苯丝氨酸可提高脑内源性乙酰胆碱水平，并且先前已表明，其可降低清醒大鼠脑内毒蕈碱胆碱能受体拮抗剂[（11）C]N-甲基吡咯烷基苯甲酸酯（[（11）C]NMPYB）的体内结合。在本研究中，采用离体解剖技术或体内微型正电子发射断层扫描（microPET）成像技术，对清醒和异氟烷麻醉的大鼠进行苯丝氨酸预处理研究。在离体解剖实验中，苯丝氨酸预处理后，清醒和麻醉动物的[（11）C]NMPYB结合均有统计学意义的10%抑制，表明使用异氟烷麻醉无有害影响。然而，在麻醉动物中进行的微型正电子发射断层扫描成像未能成功证明在相同的苯丝氨酸治疗方案后[（11）C]NMPYB结合受到抑制。这些结果表明，在少数受试者中，离体解剖可能是一种更敏感的实验方法，用于确定在这种神经递质竞争脑受体位点模型中体内放射性示踪剂结合的微小变化。
