Positron Emission Tomography (PET), as a non-invasive translatable imaging technology, can be incorporated into various stages of the CNS drug discovery process to provide valuable information for key preclinical and clinical decision-making. Novel CNS PET ligand discovery efforts in the industry setting, however, are facing unique challenges associated with lead design and prioritization, and budget constraints. In this review, three strategies aiming toward improving the central nervous system (CNS) PET ligand discovery process are described: first, early determination of receptor density (Bmax) and bio-distribution to inform PET viability and resource allocation; second, rational design and design prioritization guided by CNS PET design parameters; finally, a cost-effective in vivo specific binding assessment using a liquid chromatography-mass spectrometry (LC-MS/MS) “cold tracer” method. Implementation of these strategies allowed a more focused and rational CNS PET ligand discovery effort to identify high quality PET ligands for neuroimaging.

中文翻译：

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促进发现新型CNS PET配体的策略。

正电子发射断层扫描（PET）作为一种非侵入性的可转换成像技术，可以并入CNS药物发现过程的各个阶段，从而为关键的临床前和临床决策提供有价值的信息。然而，在行业环境中，新型CNS PET配体发现工作正面临着与潜在客户设计和优先级划分以及预算限制相关的独特挑战。在这篇综述中，描述了三种旨在改善中枢神经系统（CNS）PET配体发现过程的策略：首先，尽早确定受体密度（Bmax）和生物分布，以告知PET生存能力和资源分配。其次，以CNS PET设计参数为指导进行合理的设计和设计优先次序；最后，使用液相色谱-质谱（LC-MS / MS）“冷示踪剂”方法进行的具有成本效益的体内特异性结合评估。这些策略的实施允许更加集中和合理的CNS PET配体发现工作，以鉴定用于神经成像的高质量PET配体。