Hayes Thomas R, Thompson Charles M, Blecha Joseph E, Gerdes John M, VanBrocklin Henry F
Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, USA.
Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, MT, USA.
J Labelled Comp Radiopharm. 2018 Dec;61(14):1089-1094. doi: 10.1002/jlcr.3688. Epub 2018 Nov 4.
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]fluoropropan-2-yl)-O-(4-nitrophenyl) methylphosphonate ([ 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-[ F]fluoro-2-propanol in the presence of DBU. The 1-[ F]fluoro-2-propanol was prepared by reaction of propylene sulfite with Kryptofix 2.2.2 and [ F] fluoride ion. The desired tracer O-(1-[ 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 [ 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 [ 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.
O-(1-氟丙-2-基)-O-(4-硝基苯基)甲基膦酸酯是一种活性有机磷酸酯（OP），它是作为化学战剂沙林的替代物开发的，能在乙酰胆碱酯酶的活性位点丝氨酸处形成类似的共价加合物。放射性标记的O-(1-[F]氟丙-2-基)-O-(4-硝基苯基)甲基膦酸酯（[F]氟沙林替代物）此前尚未制备。在本文中，我们报道了首次通过双-(4-硝基苯基)甲基膦酸酯与1-[F]氟-2-丙醇在DBU存在下反应来放射性合成这种示踪剂。1-[F]氟-2-丙醇是通过亚硫酸丙烯与穴醚2.2.2和[F]氟离子反应制备的。基于起始的[F]氟离子，以2.4%±0.6%的产率（n = 5，合成开始后65分钟）获得了放射性化学纯度>98%的所需示踪剂O-(1-[F]氟丙-2-基)-O-(4-硝基苯基)甲基膦酸酯，摩尔活度为49.9 GBq/μmol（1.349±0.329 Ci/μmol，n = 3）。这种新的简便放射性合成方法常规地提供了足够量的高放射性化学纯度的[F]氟沙林替代物，这将进一步推动该示踪剂作为一种新型放射性标记的OP乙酰胆碱酯酶抑制剂的开发，用于在体内通过PET成像评估OP的作用模式。
