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 光子发射计算机断层扫描（SPECT）是核 使神经递质研究成为可能的医学技术 受体在活体动物和人类，但缺乏合适的 一些神经递质系统的放射性示踪剂限制了 这些技术的实用性。在过去的一年里， A-85380的卤代衍生物 [-3-（2（S）-氮杂环丁烷甲氧基）吡啶]的合成，并对三种 具有作为烟碱类放射性示踪剂的特殊前景的化合物 乙酰胆碱受体（nAChR）。5-碘-， A-85380的5-溴-和2-和6-氟类似物， 进入大脑，紧密地和选择性地结合到 nAChRs在大脑中占主导地位，并与 多巴胺奖励系统。此外，这些化合物是以下顺序： 比目前使用的放射性示踪剂或新示踪剂更安全 衍生自地棘蛙素。放射性标记的合成 5-[I-123/125]以及2-和6-[F-18] A-85380产生示踪剂， 高具体活动。一系列非人类灵长类动物的研究 证明了新的放射性示踪剂可以成像nAChRs， PET或SPECT成像技术， 可见的生物效应。这些新的nAChRs将是有益的， 用于研究烟草依赖的机制， 神经退行性疾病另一个目标是改善我们的 用于测定受体-配体的PET数据的定量分析 约束力使用建模技术结合分析两者 实验[C-11]-雷氯必利PET数据以及 计算机模拟数据，我们开发了一个简单的程序， 校正由于部分体积误差引起的伪影。不需要的 结合潜力估计值与结构尺寸的相关性可以 通过使用仅需要测量 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.