Radiosynthesis of the anticancer nucleoside analogue Trifluridine using an automated 18F-trifluoromethylation procedure.
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Authors
King, A
Doepner, A
Turton, D
Ciobota, DM
Da Pieve, C
Wong Te Fong, A-C
Kramer-Marek, G
Chung, Y-L
Smith, G
Doepner, A
Turton, D
Ciobota, DM
Da Pieve, C
Wong Te Fong, A-C
Kramer-Marek, G
Chung, Y-L
Smith, G
Document Type
Journal Article
Date
2018-04-25
Date Accepted
2018-03-16
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.
Citation
Organic & biomolecular chemistry, 2018, 16 (16), pp. 2986 - 2996
Source Title
Publisher
ROYAL SOC CHEMISTRY
ISSN
1477-0520
eISSN
1477-0539
Research Team
PET Radiochemistry
Preclinical Molecular Imaging
Radioisotope Physics
Preclinical Molecular Imaging
Radioisotope Physics