ACS Chemical Neuroscience p. 3007 - 3014 (2018)
Update date:2022-09-26
Topics:
Neumann, Kiel D.
Blecha, Joseph E.
Hayes, Thomas R.
Huynh, Tony
Chao, Chih-Kai
Guilloteau, Nicolas
Zinn, Kurt R.
Vanbrocklin, Henry F.
Thompson, Charles M.
Gerdes, John M.
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 the in vivo mode 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 by ex vivo biodistribution and in vivo dynamic positron emission tomography (PET) imaging in na?ve (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.
View MoreXinjiang Fufeng Biotechnologies Co., Ltd.
Contact:+86-539-7287111
Address:GANQUANPU INDUSTRIAL PARK, ECONOMIC AND TECHNOLOGICAL DEVELOPMENT AREA (TOUTUNHE DISTRICT) OF URUMQI
Beijing Mesochem Technology Co.,LTD
website:http://www.mesochem.com
Contact:0086-10-57862036
Address:2301, Floor 23, Building 9 Lippo Plaza, Yard 8 Ronghua Middle Road, ETDZ, Beijing, China
Hangzhou Reb Technology Co., Ltd.
Contact:571-81902596
Address:Room 502,Buil.5,No.1 Xi Yuan Rd. The West Lake Science&Technology Park, Hangzhou,Zhejiang,China.
ZHIJIANG ZENVA SINO COMMERCE AND TRADE CO., LTD.
website:http://www.zenvasino.com
Contact:+86-138-72658998
Address:Shibeishan Road,Zhijiang, Hubei, China
Contact:86-25-58619180
Address:Nanjing High-Tech Zone 10 Xinghuo Road Pukou District Nanjing, Jiangsu 210061 The People's Republic of China
Doi:10.1021/ja01636a051
(1954)Doi:10.1016/j.bmcl.2004.05.044
(2004)Doi:10.1016/S0040-4039(00)92793-X
(1980)Doi:10.1007/BF00957722
(1982)Doi:10.1039/b405015k
(2004)Doi:10.1021/jacs.5b00939
(2015)