Stehouwer Jeffrey, Chopra Arvind
Department of Radiology,, Center for Systems Imaging,, Emory University
National Center for Biotechnology Information, NLM, NIH, Bethesda, MD 20894
Serotonin (5-hydroxytryptamine (5HT)) is a neurotransmitter that is transported across the cell membrane by the serotonin transporter (SERT or 5HTT) (1) and is expressed in several tissues of the body, such as those of the brain, lungs (2-4), bone (5, 6), gastrointestinal tract (7), blood platelets (8, 9), and the cardiovascular system (10-12). Within the brain, the SERT is present primarily on the presynaptic neurons (13-15), and a high density of these transporters has been detected in the midbrain, caudate, putamen, thalamus, hypothalamus, pons, medulla and amygdala; by comparison, a lower density of the SERT is found in the cortex (16-22). Alterations in serotonergic neurotransmission and SERT density in the brain have been implicated in the pathophysiology of depression and schizophrenia and may lead to suicide (23-26). Investigators have developed and evaluated the biological activity of several selective serotonin reuptake inhibitors (SSRIs) for the treatment of these neurological conditions (27-30). Several SSRIs approved by the United States Food and Drug Administration (FDA) are available commercially for the treatment of SERT-related conditions. Positron emission tomography (PET) imaging is often used as an investigational tool to measure the SERT density and SSRI occupancy of the transporter (these are approved by the FDA as biomarkers) (31-33), and it is considered a suitable technique to study the pathophysiology of depression and to monitor (34) or develop new SERT therapeutics (35-37). In earlier studies it was shown that a I-labeled nortropane cocaine analog, 2β-carbomethoxy-3β-(4´-(()-2-[I]iodoethenyl)phenyl)nortropane ([I]ZIENT), had a high affinity for the human SERT and was suitable for the visualization of this transporter in non-human primates with single-photon emission computed tomography (38). In a continuing effort to develop alternate probes and tracers that can generate superior high-resolution images of the transporter, ZIENT was labeled with C (to obtain [C]ZIENT) and its binding selectivity for the SERT was investigated (39). In addition, the investigators used PET to evaluate the tracer for imaging of the transporter in anesthetized cynomolgus monkeys and conscious rhesus monkeys.
血清素（5-羟色胺（5HT））是一种神经递质，它通过血清素转运体（SERT或5HTT）跨细胞膜运输（1），并在身体的多个组织中表达，如大脑、肺（2-4）、骨骼（5,6）、胃肠道（7）、血小板（8,9）和心血管系统（10-12）。在大脑中，SERT主要存在于突触前神经元上（13-15），并且在中脑、尾状核、壳核、丘脑、下丘脑、脑桥、延髓和杏仁核中检测到这些转运体的高密度分布；相比之下，在皮质中发现SERT的密度较低（16-22）。大脑中血清素能神经传递和SERT密度的改变与抑郁症和精神分裂症的病理生理学有关，可能导致自杀（23-26）。研究人员已经开发并评估了几种选择性血清素再摄取抑制剂（SSRI）的生物活性，用于治疗这些神经系统疾病（27-30）。美国食品药品监督管理局（FDA）批准的几种SSRI已在市场上用于治疗与SERT相关的疾病。正电子发射断层扫描（PET）成像通常用作研究工具，以测量转运体的SERT密度和SSRI占有率（这些已被FDA批准为生物标志物）（31-33），并且它被认为是研究抑郁症病理生理学以及监测（34）或开发新的SERT治疗药物（35-37）的合适技术。在早期研究中表明，一种I标记的去甲托烷可卡因类似物，2β-甲氧羰基-3β-（4´-（（）-2-[I]碘乙烯基）苯基）去甲托烷（[I]ZIENT），对人SERT具有高亲和力，并且适用于用单光子发射计算机断层扫描在非人类灵长类动物中可视化这种转运体（38）。为了持续努力开发能够生成转运体 superior高分辨率图像的替代探针和示踪剂，ZIENT用C标记（以获得[C]ZIENT）并研究其对SERT的结合选择性（39）。此外，研究人员使用PET评估该示踪剂在麻醉的食蟹猴和清醒的恒河猴中对转运体成像的效果。
