Radiosynthesis of O-(1-[ 18 F]fluoropropan-2-yl)-O-(4-nitrophenyl)methylphosphonate: A novel PET tracer surrogate of sarin.

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-[ ¹⁸ F]fluoropropan-2-yl)-O-(4-nitrophenyl) methylphosphonate ([ ¹⁸ F] 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-[ ¹⁸ F]fluoro-2-propanol in the presence of DBU. The 1-[ ¹⁸ F]fluoro-2-propanol was prepared by reaction of propylene sulfite with Kryptofix 2.2.2 and [ ¹⁸ F] fluoride ion. The desired tracer O-(1-[ ¹⁸ F]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 [ ¹⁸ F] fluoride ion and a molar activity of 49.9 GBq/μmol (1.349 ± 0.329 Ci/μmol, n = 3). This new facile radiosynthesis routinely affords sufficient quantities of [ ¹⁸ F] 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.
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