Radiosynthesis of 2-deoxy-2-[18F]fluorothymidine ([18F]FT), a Putative PET Agent for Imaging HSV-TK Expression

Title: Radiosynthesis of 2-deoxy-2-[18F]fluorothymidine ([18F]FT), a Putative PET Agent for Imaging HSV-TK Expression

Volume: 2 Issue: 1

Author(s): William Sun, John Wilson, Piyush Kumar, Edward Knaus and Leonard Wiebe

Affiliation:

Keywords: Fluorodeoxythymidine, 2'-deoxy-2'-[18F]fluorothymidine, ([18F]FT), [18F]radiofluorination, transgene imaging, herpes simplex thymidine kinase, HSV-TK

Abstract: Radiolabelled nucleosides have potential applications as cell proliferation markers and as substrates for the Herpes simplex thymidine kinase (HSV-TK) reporter gene used in gene therapy. 2-Deoxy-2-[18F]fluorothymidine ([18F]FT) is highly-selective for HSV-TK relative to mammalian TK and is therefore of interest as a gene therapy reporter probe. [18F]FT was prepared via the SN 2 displacement of nosyl on 3-tert-butoxycarbonyl-1-(3,5-di-O-benzoyl-2-O-p-nitrophenylsulfonyl- β-D-arabinofuranosyl)thymine by [18F]fluoride anion, followed by deprotection. This radiofluorination precursor was synthesized from commercially-available 5-methyluridine in 11.5 % chemical yield (6 steps; Scheme 2). Fluorination of the nosylate using cyclotron-produced [18F]fluoride as the no-carrier-added activated K[18F]F-Kryptofix222 complex in acetonitrile at 95 °C, with a reaction time of 10 min, afforded crude [18F]FT in radiochemical yields (RCY) ranging from 4.2 to 15.6 percent (9.2 ± 3.8 %; n = 20). Radio TLC of the crude radiofluorinated product showed 36 to 78 percent (59.1 ± 17.2 %; n = 20) [18F]FT, recovered with radiochemical purity of 88 to 98 percent (93.8 ± 3.2 %; n = 20). Using a GE TracerLab FX synthesis unit and a manually-loaded HPLC, synthesis and purification times of 60 ± 5 min afforded overall recovered radiochemical yields averaging 5.5 ± 1.9 % (n = 20). The identity of [18F]FT was confirmed by TLC co-development, and HPLC co-elution with authentic FT. An authentic sample of reference 2-deoxy-2-fluorothymidine (FT) was prepared by direct fluorination of the 2-arabino compound 1-(3,5-di-O-trityl-β-D-arabinofuranosyl)thymine with DAST, followed by removal of the trityl protecting groups with trifluoroacetic acid, in 4 steps from 2,2-anhydro-1-(β-D-arabinofuranosyl)thymine, in 43 % overall chemical yield.

Cite this article as:

Sun William, Wilson John, Kumar Piyush, Knaus Edward and Wiebe Leonard, Radiosynthesis of 2-deoxy-2-[18F]fluorothymidine ([18F]FT), a Putative PET Agent for Imaging HSV-TK Expression, Current Radiopharmaceuticals 2009; 2 (1) . https://dx.doi.org/10.2174/1874471010902010075