Divergent synthesis of organophosphate [11C]VX- and [11C]Sarin-surrogates from a common set of starting materials

Thomas R Hayes; Joseph E Blecha; Charles M Thompson; John M Gerdes; Henry F VanBrocklin

doi:10.1016/j.apradiso.2019.05.033

Divergent synthesis of organophosphate [¹¹C]VX- and [¹¹C]Sarin-surrogates from a common set of starting materials

Appl Radiat Isot. 2019 Sep:151:182-186. doi: 10.1016/j.apradiso.2019.05.033. Epub 2019 May 24.

Authors

Thomas R Hayes¹, Joseph E Blecha¹, Charles M Thompson², John M Gerdes², Henry F VanBrocklin³

Affiliations

¹ Department of Radiology and Biomedical Imaging, University of California - San Francisco, 185 Berry St. Suite 350, San Francisco, CA, 94107, United States.
² Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, MT, 59812, United States.
³ Department of Radiology and Biomedical Imaging, University of California - San Francisco, 185 Berry St. Suite 350, San Francisco, CA, 94107, United States. Electronic address: [email protected].

Abstract

Radiolabeled 1-[¹¹C]ethyl, 4-nitrophenyl methylphosphonate (VX surrogate) and 2-[¹¹C]-propanyl, 4-nitrophenyl methylphosphonate (sarin surrogate) were developed as organophosphate (OP) tracers. The [¹¹C]ethyl- and [¹¹C]isopropyl-iodide radiolabeled synthons were obtained by temperature controlled, in loop reactions of [¹¹C]CO₂ with MeMgBr followed by reduction with LiAlH₄, then reaction with HI. Distillation of the [¹¹C]alkyl iodides into a solution of hydrogen (4-nitrophenyl)methylphosphonate and cesium carbonate afforded the desired tracers in >95% radiochemical purity, yields from [¹¹C]CO₂ of 1-3% and 1.7-15.1 GBq/mmol molar activities.

Keywords: [(11)C]VX surrogate; [(11)C]ethyl iodide; [(11)C]isopropyl iodide; [(11)C]sarin surrogate; acetylcholinesterase; organophosphate.

Grants and funding

U01 NS092495/NS/NINDS NIH HHS/United States