Issue 16, 2018

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

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

Supplementary files

Article information

Article type
Paper
Submitted
19 Feb 2018
Accepted
16 Mar 2018
First published
09 Apr 2018
This article is Open Access
Creative Commons BY license

Org. Biomol. Chem., 2018,16, 2986-2996

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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