Radiosynthesis of the tumor hypoxia marker [(18)F]TFMISO via O-[(18)F]trifluoroethylation reveals a striking difference between trifluoroethyl tosylate and iodide in regiochemical reactivity toward oxygen nucleophiles Journal Article

   

Authors:	Suehiro, M.; Yang, G.; Torchon, G.; Ackerstaff, E.; Humm, J.; Koutcher, J.; Ouerfelli, O.
Article Title:	Radiosynthesis of the tumor hypoxia marker [(18)F]TFMISO via O-[(18)F]trifluoroethylation reveals a striking difference between trifluoroethyl tosylate and iodide in regiochemical reactivity toward oxygen nucleophiles
Abstract:	The MRI hypoxia marker trifluoromisonidazole (TFMISO) [1-(2-nitro-1H- imidazol-1-yl)-3-(2,2,2-trifluoroethoxy)propan-2-ol] was successfully labeled with 18F to expand its role into a bimodal PET/MRI probe. 18F-Labeling was achieved via a three-step procedure in which 2,2,2-[18F]trifluoroethyl p-toluenesulfonate prepared by 18F-19F exchange served as the [18F] trifluoroethylating agent. The O-[18F]trifluoroethylation reaction proceeded efficiently to give the intermediate 1,2-epoxy-3-(2,2,2-[ 18F]trifluoroethoxy)propane, with approximately 60% of 18F incorporated from the tosylate precursor, which was condensed with 2-nitroimidazole to yield [18F]TFMISO. Approximately 40% of the [18F]trifluoroethyl tosylate precursor was converted into the final product. In stark contrast, 2,2,2-[18F]trifluoroethyl iodide failed to produce [18F]TFMISO, giving instead 1,1-[18F]difluoro- 2-iodoethoxy and 1-[18F]fluoro-2-iodovinyloxy analogs of [ 18F]TFMISO. Thus, this investigation has identified 2,2,2-[ 18F]trifluoroethyl tosylate as an excellent [18F] trifluoroethylating agent, which can convert efficiently an alcohol into the corresponding [18F]trifluoroethyl ether. © 2011 Published by Elsevier Ltd.
Keywords:	unclassified drug; nuclear magnetic resonance imaging; positron emission tomography; biological marker; oxygen; drug synthesis; hypoxia; isotope labeling; tracer; tumor; fluorine 18; chemical reaction; toluenesulfonic acid derivative; radiochemistry; chemical modification; nucleophile; fluorine; 2,2,2-[18f]trifluoroethyl tosylate; 18f-labeled trifluoromisonidazole ([18f]tfmiso); bimodal mri and pet hypoxia marker; o-[18f]trifluoroethylation; 1 fluoro 2 iodovinyloxy f 18; 1,1 difluoro 2 iodoethoxy f 18; 1,2 epoxy 3 (2,2,2 trifluoroethoxy)propane f 18; 2 nitroimidazole; 2,2,2 trifluoroethyl 4 toluenesulfonate f 18; 2,2,2 trifluoroethyl tosylate f 18; trifluoroethyl tosylate; trifluoroethyl tosylate f 18; trifuoromisonidazole f 18
Journal Title:	Bioorganic & Medicinal Chemistry
Volume:	19
Issue:	7
ISSN:	0968-0896
Publisher:	Pergamon-Elsevier Science Ltd
Date Published:	2011-04-01
Start Page:	2287
End Page:	2297
Language:	English
DOI:	10.1016/j.bmc.2011.02.026
PROVIDER:	scopus
PUBMED:	21398131
PMCID:	PMC4072420
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-79953187907&partnerID=40&md5=86454e2d8416b13fa157f06bbe719979
Notes:	--- - "Export Date: 23 June 2011" - "CODEN: BMECE" - "Source: Scopus"

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