DEVELOPMENT OF NEW PET AND SPECT RADIOTRACERS AND NEW APPROACHES TO PET DATA

正电子发射断层扫描(PET)和单次扫描 光子发射计算机断层扫描(SPECT)是核的 使神经递质研究成为可能的医学技术 活体动物和人类中的受体，但缺乏合适的 一些神经递质系统的放射性示踪剂限制了 这些技术的有用性。在过去的一年里，一系列 A-85380的卤代衍生物 合成了[-3-(2(S)-氮杂二甲氧基)吡啶]. 作为烟碱放射性示踪剂的特殊前景的化合物 鉴定了乙酰胆碱受体(NAChRs)。5-碘-， 5-溴-以及A-85380的2-和6-氟类似物，迅速 进入大脑，紧密地和选择性地结合在一起 在大脑中占主导地位的nAChRs，与 多巴胺奖励系统。此外，这些化合物是 比目前使用的放射性示踪剂或新示踪剂更安全 源自依巴替丁。放射性标记化合物的合成 5-[I-123/125]和2-和6-[F-18]A-85380产生示踪剂 高比活度。一系列非人灵长类动物研究 演示了新的放射性示踪剂可以用来成像nAChRs PET或SPECT成像技术，无需生产 可观察到的生物效应。这些新的nAChR将是有益的 用于研究烟草依赖的机制和 神经退行性疾病。另一个目标是改善我们的 用于受体-配体检测的PET数据的定量分析 有约束力的。使用结合了对两者的分析的建模技术 实验[C-11]-拉氯普利PET数据以及 计算机模拟数据，我们开发了一个简单的程序来 由于部分体积误差而产生的伪影得到纠正。不需要的人 结合势估计与结构大小的相关性可以是 通过使用一种只需要测量 大脑的结构尺寸和前景与背景的对比度 图像。

Positron emission tomography (PET) and single photon emission computed tomography (SPECT) are nuclear medicine techniques that enable the study of neurotransmitter receptors in living animals and humans, but the lack of suitable radiotracers for some neurotransmitter systems has limited the usefulness of these techniques. In the past year, a series of halogenated derivatives of A-85380 [-3-(2(S)-azetidinylmethoxy)pyridine] were synthesized and three compounds with exceptional promise as radiotracers for nicotinic acetylcholine receptors (nAChRs) were identified. The 5-iodo-, 5-bromo- and the 2- and 6-fluoro analogs of A-85380, rapidly entered the brain, bound tightly and selectively to the subtype of nAChRs that predominates in the brain and is linked to the dopamine reward system. Further, these compounds are orders of magnitude safer than currently used radiotracers or new tracers derived from epibatidine. The synthesis of radiolabeled 5-[I-123/125] and 2- and 6-[F-18] A-85380 yielded tracers with high specific activities. A series of nonhuman primate studies demonstrated that the new radiotracers can image nAChRs using either PET or SPECT imaging techniques without producing observable biological effects. These new nAChRs will be beneficial for studying mechanisms of tobacco dependence and neurodegenerative diseases. Another goal has been to improve our quantitative analysis of PET data for assaying receptor-ligand binding. Using modeling techniques incorporating analyses of both experimental [C-11]-raclopride PET data as well as computer-simulated data, we developed a simple procedure for correction of the artifact due to partial volume error. The unwanted correlation of binding potential estimates with structure size can be eliminated by using a technique requiring only measurements of structure size and foreground to background contrast on the brain images.