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Issue 16, 2018
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Radiosynthesis of the anticancer nucleoside analogue Trifluridine using an automated 18F-trifluoromethylation procedure

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Abstract

Trifluoromethyl groups are widespread in medicinal chemistry, yet there are limited 18F-radiochemistry techniques available for the production of the complementary PET agents. Herein, we report the first radiosynthesis of the anticancer nucleoside analogue trifluridine, using a fully automated, clinically-applicable 18F-trifluoromethylation procedure. [18F]Trifluridine was obtained after two synthetic steps in <2 hours. The isolated radiochemical yield was 3% ± 0.44 (n = 5), with a radiochemical purity >99%, and a molar activity of 0.4 GBq μmol−1 ± 0.05. Biodistribution and PET-imaging data using HCT116 tumour-bearing mice showed a 2.5 %ID g−1 tumour uptake of [18F]trifluridine at 60 minutes post-injection, with bone uptake becoming a prominent feature thereafter. In vivo metabolite analysis of selected tissues revealed the presence of the original radiolabelled nucleoside analogue, together with deglycosylated and phosphorylated [18F]trifluridine as the main metabolites. Our findings suggest a potential role for [18F]trifluridine as a PET radiotracer for elucidation of drug mechanism of action.

Graphical abstract: Radiosynthesis of the anticancer nucleoside analogue Trifluridine using an automated 18F-trifluoromethylation procedure

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Publication details

The article was received on 19 Feb 2018, accepted on 16 Mar 2018 and first published on 09 Apr 2018


Article type: Paper
DOI: 10.1039/C8OB00432C
Citation: Org. Biomol. Chem., 2018,16, 2986-2996
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    Radiosynthesis of the anticancer nucleoside analogue Trifluridine using an automated 18F-trifluoromethylation procedure

    A. King, A. Doepner, D. Turton, D. M. Ciobota, C. Da Pieve, A. Wong Te Fong, G. Kramer-Marek, Y. Chung and G. Smith, Org. Biomol. Chem., 2018, 16, 2986
    DOI: 10.1039/C8OB00432C

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