There is a unique in vivo interplay involving the mechanism of inactivation of acetylcholinesterase (AChE) by toxic organophosphorus (OP) compounds and the restoration of AChE activity by oxime antidotes. OP compounds form covalent adducts to this critical enzyme target and oximes are introduced to directly displace the OP from AChE. For the most part, the in vivo inactivation of AChE leading to neurotoxicity and antidote-based therapeutic reversal of this mechanism are well understood, however, these molecular-level events have not been evaluated by dynamic imaging in living systems at millimeter resolution. A deeper understanding of these critically, time-dependent mechanisms is needed to develop new countermeasures. To address this void and to help accelerate the development of new countermeasures, positron-emission tomography (PET) has been investigated as a unique opportunity to create platform technologies to directly examine the interdependent toxicokinetic/pharmacokinetic and toxicodynamic/pharmacodynamic features of OPs and oximes in real time within live animals. This review will cover two first-in-class PET tracers representing an OP and an oxime antidote, including their preparation, requisite pharmacologic investigations, mechanistic interpretations, biodistribution and imaging.

中文翻译：

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正电子发射断层成像研究有机磷酸酯化学威胁和肟对策。

有一种独特的体内相互作用，涉及通过有毒有机磷（OP）化合物使乙酰胆碱酯酶（AChE）失活以及通过肟解毒剂恢复AChE活性的机制。OP化合物与该关键酶靶标形成共价加合物，并引入肟直接从AChE取代OP。在大多数情况下，AChE在体内的失活导致神经毒性和该机制的基于解毒剂的治疗性逆转是众所周知的，但是，这些分子水平的事件尚未通过毫米级分辨率的动态成像在活体系统中进行评估。需要对这些关键的，与时间有关的机制有更深入的了解，以制定新的对策。为了解决这一空白并帮助加快制定新的对策，正电子发射断层扫描（PET）已被研究为创造平台技术来直接检查活体动物中OP和肟相互依赖的毒物动力学/药代动力学和毒物动力学/药效学特征的独特机会。这篇综述将涵盖代表OP和肟解毒剂的两个一流的PET示踪剂，包括它们的制备，必要的药理研究，机理解释，生物分布和成像。