Radiosynthesis, ex Vivo Biodistribution, and in Vivo Positron Emission Tomography Imaging Evaluations of [11C]2-Pyridinealdoxime Methiodide ([11C]2-PAM): A First-In-Class Antidote Tracer for Organophosphate Intoxication.
Radiosynthesis, ex Vivo Biodistribution, and in Vivo Positron Emission Tomography Imaging Evaluations of [11C]2-Pyridinealdoxime Methiodide ([11C]2-PAM): A First-In-Class Antidote Tracer for Organophosphate Intoxication.
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[11C]2-吡啶醛肟甲硫醚 ([11C]2-PAM) 的放射合成、离体生物分布和体内正电子发射断层扫描成像评估：一种用于有机磷中毒的一流解毒示踪剂。
DOI：
10.1021/acschemneuro.8b00212
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发表时间：
2018
影响因子：
5
通讯作者：
Gerdes,JohnM
中科院分区：
文献类型：
--
作者：
Neumann,KielD;Blecha,JosephE;Hayes,ThomasR;Huynh,Tony;Chao,Chih-Kai;Guilloteau,Nicolas;Zinn,KurtR;VanBrocklin,HenryF;Thompson,CharlesM;Gerdes,JohnM
2-Pyridinealdoxime methiodide (2-PAM) is a widely used antidote for the treatment of organophosphorus (OP) exposure that reactivates the target protein acetylcholinesterase. Carbon-11 2-PAM was prepared to more fully understand thein vivomode of action, distribution, and dynamic qualities of this important countermeasure. Alkylation of 2-pyridinealdoxime with [11C]CH3I provided the first-in-class [11C]2-PAM tracer in 3.5% decay corrected radiochemical yield from [11C]CH3I, >99% radiochemical purity, and 4831 Ci/mmol molar activity. [11C]2-PAM tracer distribution was evaluated byex vivobiodistribution andin vivodynamic positron emission tomography (PET) imaging in naïve (OP exposure deficient) rats. Tracer alone and tracer coinjected with a body mass-scaled human therapeutic dose of 30 mg/kg nonradioactive 2-PAM demonstrated statistically similar tissue and blood distribution profiles with the greatest uptake in kidney and significantly lower levels in liver, heart, and lung with lesser amounts in blood and brain. The imaging and biodistribution data show that radioactivity uptake in brain and peripheral organs is rapid and characterized by differential tissue radioactivity washout profiles. Analysis of arterial blood samples taken 5 min after injection showed ∼82% parent [11C]2-PAM tracer. The imaging and biodistribution data are now established, enabling future comparisons to outcomes acquired in OP intoxicated rodent models.
