Novel Tc99m-Chelates for Imaging Monoamine Transporters

本研究建议中描述的研究涉及连接到哌啶药效团的新型99 mTc螯合物的设计和制备。这种放射性配体有望表现出诊断和管理单胺系统神经功能障碍的潜力。因此，它们将通过提供用于诊断和管理帕金森病的单光子计算机断层扫描（SPECT）试剂，与我们的新型哌啶药效团连接的螯合物，提供改善人类健康状况的能力。哌啶药效团可以是多巴胺转运蛋白的SPECT试剂，也可以是血清素和去甲肾上腺素转运蛋白的SPECT试剂。所制备的配体最初将被标记为作为99 mTc的非放射性模型的氧代（oxo）物质。将测定对单胺转运蛋白的体外活性，发现对单胺转运蛋白表现出高结合亲和力和选择性的化合物将用99 mTc进行放射性标记。拟议的商业应用：由于目前没有SPECT试剂可用于诊断和管理涉及单胺能神经传递功能障碍的疾病，例如帕金森病、ADD/ADHD和抑郁症。该提案的成功完成将最终导致基于99 mTc的SPECT试剂的开发和销售，用于诊断和管理此类疾病。

The studies described in this research proposal involve the design and preparation of novel 99mTc chelates linked to a piperidine pharmacophore. Such radioligands would be expected to exhibit potential for the diagnosis and management of neurological dysfunctions in monoamine systems. As such they will provide the ability to improve state of human health care by affording single photon computed tomography (SPECT) agents for diagnosis and management of Parkinson's disease, chelates linked to our novel piperidine pharmacophore. The piperidine pharmacophore can be SPECT agents for the dopamine transporter, but also the serotonin and norepinephrine transporters. The ligands prepared will initially be labeled as rhenium(oxo) species as a non-radioactive model for 99mTc. The in vitro activity at the monoamine transporters will be determined and compounds found to exhibit high binding affinity and selectivity for the monoamine transporters will be radiolabeled with 99mTc. PROPOSED COMMERCIAL APPLICATIONS: As no SPECT agents are currently available for the diagnosis and management of diseases involving dysfunctions in monoaminergic neurotransmission, such as Parkinson's disease, ADD/ADHD and depression. The successful completion of this proposal will ultimately lead to the development and marketing of 99mTc based SPECT agents for the diagnosis and management of such diseases.