PET RADIOTRACERS FOR IMAGING THE DOPAMINE D3 RECEPTOR

描述(由申请人提供)：PET成像研究测量多巴胺D2类受体功能的变化，历史上使用的放射性示踪剂无法区分D2/和D3受体。例如，[11C]雷氯普利、[18F]FolyPride和[11C]PHNO与多巴胺D2和D3受体具有高亲和力。因此，用这些放射性示踪剂获得的“D2受体结合势”的测量包括D2和D3受体密度的组合。许多研究表明，在各种中枢神经系统疾病中，D2和D3受体以相反的方式调节。例如，据报道，帕金森病死后脑标本腹侧纹状体的D3受体减少了45%，尾状核/壳核的D2受体增加了15%。其他研究表明，在长期接触可卡因后，大脑样本中D3受体增加，D2受体减少。因此，发展对D3和D2受体具有高亲和力的放射性示踪剂，反之亦然，将引起PET成像和神经科学研究领域的极大兴趣，因为它将使D2和D3受体在各种中枢神经系统疾病中的独立测量成为可能。我们小组目前(通过PA-03-112)获得资金，用于开发对D2和D3受体具有高亲和力和选择性的PET放射性示踪剂。目前研究项目的功能是开发针对D3受体的选择性PET放射性示踪剂，这将补充我们正在进行的开发D2选择性放射性示踪剂的研究。我们研究工作的最终目标是开发一种新的策略来成像各种中枢神经系统疾病中D3和D2受体的变化。

DESCRIPTION (provided by applicant): PET imaging studies measuring the change in dopamine D2-class of receptors function have historically used radiotracers that are not capable of discriminating between D2/ and D3 receptors. For example, [11C] raclopride, [18F] fallypride and [11C] PHNO bind with high affinity to dopamine D2 and D3 receptors. Therefore, measurement of "D2 receptor binding potential" obtained with these radiotracers consists of a composite of D2 and D3 receptor density. A number of studies have provided evidence suggesting that D2 and D3 receptors are regulated in an opposing manner in a variety of CNS disorders. For example, it has been reported that there is a 45% reduction in D3 receptors in the ventral striatum and a 15% increase in D2 receptors the caudate/putamen of postmortem brain samples of Parkinson's Disease. Other studies have shown an increase in D3 receptors and a decrease in D2 receptors in brain samples obtained following chronic exposure to cocaine. Therefore, the development of radiotracers having a high affinity for D3 versus D2 receptors, and vice versa, would be of tremendous interest to the PET imaging and neuroscience research community since it would enable the independent measurement of D2 and D3 receptors in a variety of CNS disorders. Our group is currently funded (through PA-03-112) to develop PET radiotracers having a high affinity and selectivity for D2 versus D3 receptors. The function of the current research project is to develop PET radiotracers selective for the D3 receptor which would complement our ongoing research in the development of D2-selective radiotracers. The ultimate goal of our research effort is to develop a novel strategy for imaging the change in D3 and D2 receptors in a variety of CNS disorders.