Spect Brain Imaging In Neuropsychiatric Disorders

单光子发射计算机断层扫描(SPECT)可以测量放射性示踪剂在脑内的三维分布。正在使用的跟踪器主要分为两类。在第一类中，示踪剂在大脑中的摄取与血流量成比例，因此可以用作神经活动的标志。第二类示踪剂与大脑中的神经递质受体结合，从而使活动反映相关神经化学的分布。虽然以前使用脑血流制剂的工作在很大程度上是成功的，但现在有了其他更灵敏的方法来测量脑血流量。因此，SPECT成像已成为我们体内神经化学的首选方法。在临床人群中，我们对三种放射性配基进行了研究。这些药物包括多巴胺D2拮抗剂IBZM、多巴胺和5-羟色胺转运体拮抗剂β-CIT和毒鼠强拮抗剂QNB。我们已经使用这些放射性配体来检测非药物精神分裂症患者神经化学功能的临床相关性，并进一步阐明抗精神病药物的作用机制。我们还完成了多发性抽动症和酒精依赖患者的多巴胺能和5-羟色胺能功能的研究。在使用这些配体的非人类灵长类动物研究中，我们测试了人类神经精神疾病模型的神经化学功能。我们还进行了非人类灵长类动物的研究，以开发新的放射性配体。这些药物包括多巴胺D1受体拮抗剂Tisch和5-羟色胺5HT2激动剂DOI。

Single photon emission computed tomography, SPECT, allows for the measurement of the 3-D distribution of radioactive tracers in brain. Tracers in use fall into two main classes. In the first class, the tracer is taken up in brain in proportion to blood flow and thus can be utilized as a marker of neural activity. The second class of tracers binds to neurotransmitter receptors in brain such that the activity then reflects the distribution of the related neurochemistry. While previous work with cerebral blood flow agents was largely successful, other more sensitive means now exist for CBF measurements. Therefore, SPECT imaging has become our procedure of choice for in vivo neurochemistry. In clinical populations, we have performed studies with three radioligands. These include the dopamine D2 antagonist IBZM, the dopamine and serotonin transporter antagonist beta-CIT, and the muscarinic antagonist QNB. We have used these radioligands to examine clinical correlates of neurochemical function in drug- free schizophrenic patients, and to further elucidate the mechanism of action of neuroleptic drugs. We have also completed studies of dopaminergic and serotonergic function in patients with Tourette's syndrome and alcohol dependence. In non-human primate studies with these ligands we have tested neurochemical function in models of human neuropsychiatric illness. We have also conducted non-human primate studies to develop new radioligands. These include TISCH, a dopamine D1 receptor antagonist, and DOI, a serotonin 5HT2 agonist.