Novel Tc99m-Chelates for Imaging Monoamine Transporters

这项研究计划中描述的研究包括设计和制备与哌啶类药效团相连的新型99mTc螯合物。这种放射性配基有望在诊断和治疗单胺系统中的神经功能障碍方面显示出潜力。因此，它们将通过提供用于诊断和治疗帕金森病的单光子计算机断层扫描(SPECT)试剂来提供改善人类健康护理状况的能力，这些试剂与我们的新型哌啶药效基团有关。哌啶类药物载体可以是多巴胺转运体的SPECT试剂，也可以是5-羟色胺和去甲肾上腺素转运体的SPECT试剂。所制备的配体最初将被标记为Re(Oxo)物种，作为99mTc的非放射性模型。单胺转运体的体外活性将被测定，发现对单胺转运体具有高结合亲和力和高选择性的化合物将被99mTc放射性标记。建议的商业应用：由于目前还没有SPECT试剂可用于诊断和治疗涉及单胺类神经传递功能障碍的疾病，如帕金森氏病、ADD/ADHD和抑郁症。这项提议的成功完成将最终导致以99mTc为基础的SPECT试剂的开发和营销，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.