Radiosynthesis of O-(1-[18F]fluoropropan-2-yl)-O-(4-nitrophenyl)methylphosphonate: A novel PET tracer surrogate of sarin
Radiosynthesis of O-(1-[18F]fluoropropan-2-yl)-O-(4-nitrophenyl)methylphosphonate: A novel PET tracer surrogate of sarin
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DOI：
10.1002/jlcr.3688
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发表时间：
2018-12-01
影响因子：
1.8
通讯作者：
VanBrocklin, Henry F.
中科院分区：
文献类型：
--
作者：
Hayes, Thomas R.;Thompson, Charles M.;VanBrocklin, Henry F.
O-(1-Fluoropropan-2-yl)-O-(4-nitrophenyl) methylphosphonate is a reactive organophosphate ester (OP) developed as a surrogate of the chemical warfare agent sarin that forms a similar covalent adduct at the active site serine of acetylcholinesterase. The radiolabeled O-(1-[F-18]fluoropropan-2-yl)-O-(4-nitrophenyl) methylphosphonate ([F-18] fluorosarin surrogate) has not been previously prepared. In this paper, we report the first radiosynthesis of this tracer from the reaction of bis-(4-nitrophenyl) methylphosphonate with 1-[F-18]fluoro-2-propanol in the presence of DBU. The 1-[F-18]fluoro-2-propanol was prepared by reaction of propylene sulfite with Kryptofix 2.2.2 and [F-18] fluoride ion. The desired tracer O-(1-[F-18]fluoropropan-2-yl)-O-(4-nitrophenyl) methylphosphonate was obtained in a >98% radiochemical purity with a 2.4% +/- 0.6% yield (n = 5, 65 minutes from start of synthesis) based on starting [F-18] fluoride ion and a molar activity of 49.9 GBq/mu mol (1.349 +/- 0.329 Ci/mu mol, n = 3). This new facile radiosynthesis routinely affords sufficient quantities of [F-18] fluorosarin surrogate in high radiochemical purity, which will further enable the tracer development as a novel radiolabeled OP acetylcholinesterase inhibitor for assessment of OP modes of action with PET imaging in vivo.
