Oxime antidotes regenerate organophosphate‐inhibited acetylcholinesterase (AChE). Although they share a common mechanism of AChE reactivation, the rate and amount of oxime that enters the brain are critical to the efficacy, a process linked to the oxime structure and charge. Using a platform based on the organophosphate [18F]‐VXS as a positron emission tomography tracer for active AChE, the in vivo distribution of [18F]‐VXS was evaluated after an LD50 dose (250 μg/kg) of the organophosphate paraoxon (POX) and following oximes as antidotes. Rats given [18F]‐VXS tracer alone had significantly higher radioactivity (two‐ to threefold) in the heart and lung than rats given LD50 POX at 20 or 60 min prior to [18F]‐VXS. When rats were given LD50 POX followed by 2‐PAM (cationic), RS194b (ionizable), or monoisonitrosoacetone (MINA) (neutral), central nervous system (CNS) radioactivity returned to levels at or above untreated naive rats (no POX), whereas CNS radioactivity did not increase in rats given the dication oximes HI‐6 or MMB‐4. MINA showed a significant, pairwise increase in CNS brain radioactivity compared with POX‐treated rats. This new in vivo dynamic platform using [18F]‐VXS tracer measures and quantifies peripheral and CNS relative changes in AChE availability after POX exposure and is suitable for comparing oxime delivery and AChE reactivation in rats.

中文翻译：

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使用示踪剂 O-(2-[ 18 F] 氟乙基)-O-( p-硝基苯基) 甲基膦酸酯 [ 18 F]-VXS 对活大鼠中肟对抗措施的正电子发射断层扫描评估

肟解毒剂可再生有机磷抑制的乙酰胆碱酯酶 (AChE)。尽管它们共享 AChE 再激活的共同机制，但进入大脑的肟的速度和数量对疗效至关重要，这一过程与肟结构和电荷有关。使用基于有机磷 [18F]-VXS 的平台作为活性 AChE 的正电子发射断层扫描示踪剂，在 LD50 剂量 (250 μg/kg) 的有机磷对氧磷 (POX) 后评估 [18F]-VXS 的体内分布) 和以下肟作为解毒剂。在 [18F]-VXS 之前 20 或 60 分钟，单独给予 [18F]-VXS 示踪剂的大鼠在心脏和肺中的放射性显着高于给予 LD50 POX 的大鼠（2-3 倍）。当大鼠被给予 LD50 POX，然后是 2-PAM（阳离子）、RS194b（可电离）或单异亚硝基丙酮 (MINA)（中性）时，中枢神经系统 (CNS) 放射性恢复到未治疗的幼稚大鼠（无 POX）或更高的水平，而给予二甲基肟 HI-6 或 MMB-4 的大鼠中，CNS 放射性没有增加。与 POX 治疗的大鼠相比，MINA 显示出中枢神经系统脑放射性显着的成对增加。这种使用 [18F]-VXS 示踪剂的新体内动态平台测量和量化 POX 暴露后 AChE 可用性的外周和 CNS 相对变化，适用于比较大鼠的肟传递和 AChE 再激活。