DOPAMINE TRANSPORTER IMAGING BY PET IN AGING AND DISEASE

已知多巴胺能系统在治疗期间经历轻度变性。 正常老化过程，并以加速的速度，在一定的运动 紊乱正电子发射断层扫描（PET）是一种非常好的 一种非侵入性测量正常人多巴胺能神经元损失的方法 由于高化学特异性， 可以使用目前可用的放射性示踪剂来实现。我们最近 开发了IIC-WIN 35，428作为成像和定量的示踪配体 多巴胺转运蛋白的含量IIC-WIN 35，428是通过无线电合成的， 11 C-甲基碘与适当脱甲基前体的反应 比活度大于1000 Ci/mmole。我们先前已经 证明11 C-WIN 35428与多巴胺转运蛋白的结合是 减少帕金森病（PD），我们现在建议延长我们的 研究结果表明，非常轻度的PD的长期目标是改善 我们对多巴胺系统缺陷的理解和PET成像 影像学方法用于PD的早期生化鉴定。该目的是 根据目前使用的神经保护治疗， 减缓帕金森病的发展早期-可能是临床前的生化 区分PD与正常个体，以及其他 疾病如进行性核上性麻痹和特发性震颤， 将允许更早的神经保护治疗机构比 仅通过临床诊断即可。 正常老化和相关的11 C-WLN 35，428结合减少是一个重要的因素。 这一建议的重点，因为一些运动障碍可能代表 加速作为正常老化过程的一部分观察到的变化。 然而，其他PET示踪剂还没有可靠地检测到年龄相关的 突触前多巴胺能神经元的损失，11 C-WIN 35，428具有 可能达到检测细微变化所需的灵敏度 多巴胺能系统中发生的变化。年龄说明- 大脑多巴胺系统的相关变化对于 了解正常的衰老是如何导致某些疾病的。为 与含多巴胺的药物相互作用的药物的开发和使用 神经元

The dopaminergic system is known to undergo mild degeneration during the course of normal aging and, at an accelerated rate, in certain movement disorders. Positron emission tomography (PET) represents an excellent method to noninvasively measure the loss of dopaminergic neurons in normal aging and movement disorders due to the high chemically specificity that can be achieved using currently available radiotracers. We have recently developed IIC-WIN 35,428 as a tracer ligand for imaging and quantitation of the dopamine transporter by PET. IIC-WIN 35,428 is radio synthesized by the reaction of 11C-methyliodide with an appropriate des-methyl precursor at a specific activity of greater than 1000 Ci/mmole. We have previously demonstrated that 11C-WIN 35428 binding to the dopamine transporter is reduced in Parkinson disease (PD), and we now propose to extend our results to the study of very mild PD with the long-term goals of improving our understanding the deficits in the dopamine system and developing a PET imaging method for the early biochemical identification of PD. This aim is significant based on the current use of neuroprotective therapy for slowing the progression of PD. The early-possibly pre-clinical biochemical discrimination of PD from normal individuals, and those with other disorders such as progressive supranuclear palsy and essential tremor, would permit earlier institution of neuroprotective therapy than is possible by clinical diagnosis alone. Normal aging and associated reductions in 11C-WLN 35,428 binding is a focus of this proposal since some movement disorders may represent acceleration of the changes observed as part of the normal aging process. Whereas other PET tracers have not reliably detected the age-associated loss of pre-synaptic dopaminergic neurons, 11C-WIN 35,428 has the potential to achieve the sensitivity needed to detect the subtle changes in the dopaminergic system that occur in normal aging. Elucidation of age- associated changes in the brain dopamine system would be significant for understanding how normal aging may predispose to certain diseases and. for the development and use of drugs that interact with dopamine-containing neurons.