PET AND SPECT IMAGING OF THE DOPAMINERGIC SYSTEM

正电子发射断层扫描（PET）或单光子发射计算机 断层扫描（SPECT）已被用作独特的非侵入性工具， 发展定量示踪动力学研究， 特定生化过程的解剖分布和速率 多巴胺能神经传递 这些技术在基础 这些领域的临床研究促使我们继续探索 用于PET和SPECT研究的新试剂。 进一步发展这些 技术取决于更有效和更有选择性的 适用于各种成像的同位素标记试剂 仪器仪表 在第一阶段，合成PET和 适用于多巴胺转运蛋白成像的SPECT试剂是 演示。 进行了初步的PET和SPECT研究， 确定了需要优化的参数， 使产品商业化。 拟议的研究寻求继续开发有前途的配体 具有治疗性PET和SPECT成像潜力， 帕金森氏症等疾病。 方法继续那些证明 成功地在我们的第一阶段计划，并将包括成像的 多巴胺转运蛋白（DAT）与[123 I] β-CIT;“试剂盒”的制备 用于快速合成[125 I]-和[123 I] β-CIT; （1 S）-（+）-β-CIT（非活性异构体），用于评估非特异性 摄取;进一步开发DAT和 可标记的β-CIT的N-氟烷基类似物的合成 18F用于PET成像或123 I用于SPECT成像。

Positron emission tomography (PET) or single photon emission computed tomography (SPECT) have been used as unique non-invasive tools for the development of quantitative tracer kinetic studies for the measurement of the anatomic distribution and rates of specific biochemical processes on dopaminergic neurotransmission. The utility of these techniques in basic and clinical research in these areas has prompted us to continue exploring new agents for PET and SPECT studies. Further development of these techniques depends upon the availability of more potent and selective agents labeled with isotopes suitable for use with varied imaging instrumentation. In Phase I, the feasibility of synthesizing PET and SPECT agents suitable for imaging the Dopamine transporter was demonstrated. Preliminary PET and SPECT studies were conducted and parameters were identified which need to be optimized in order to commercialize the products. Proposed studies seek to continue the development of promising ligands with therapeutic PET and SPECT imaging potential for such neurological disorders as Parkinson's Disease. Approaches continue those proved successful in our Phase I program, and will include the Imaging of the Dopamine Transporter (DAT) with [123I]beta-CIT; the preparation of a "kit" for the rapid synthesis of [125I]- and [123I]beta-CIT; the synthesis of (1S)-(+)-beta-CIT (Inactive Isomer) for the assessment of non-specific uptake; the further development of selective probes for the DAT and the synthesis of N-Fluoroalkyl analogs of beta-CIT which can be labeled with 18F for PET imaging or 123I for SPECT imaging.