Synthesis, radiosynthesis and in vitro studies on novel hypoxia PET tracers incorporating [18F]FDR
MetadataShow full item record
Altmetrics Handle Statistics
Altmetrics DOI Statistics
We report the synthesis of five radiotracers incorporating different oxyamine spacers between the hypoxia‐reactive 2‐nitroimidazole moiety and the 5‐[18F]‐fluorodeoxyribose ([18F]FDR, 12 ) prosthetic group: three linear alkyl chains with 3, 5, 7 carbon atoms ( 15 a – c ), a cyclopropyl ring ( 15 d ) and a 1,4‐disubstituted‐1,2,3‐triazole ( 15 e ). Experiments in hypoxic cells showed that 15 d displays superior uptake kinetics – and similar selectivity for hypoxic cells – relative to the gold standard hypoxia tracers [18F]fluoroazomycin arabinoside ([18F]FAZA) and [18F]fluoromisonidazole ([18F]FMISO). Lipophilicity and structural rigidity have strong influence on the selectivity of tracers 15 towards hypoxic cells: the lead tracer 15 d displays a logP=0.38 and the most rigid spacer. A sixth radiotracer ( 15 f ), with a 2‐H‐imidazole replacing the 2‐nitroimidazole moiety of 15 d , was used to demonstrate that the cyclopropyl group does not play a meaningful role in the sensitivity towards hypoxia.
Zanda , M , Musolino , M , Fleming , I N , Schweiger , L F , O’Hagan , D & Dall’Angelo , S 2021 , ' Synthesis, radiosynthesis and in vitro studies on novel hypoxia PET tracers incorporating [ 18 F]FDR ' , European Journal of Organic Chemistry , vol. Early View . https://doi.org/10.1002/ejoc.202001670
European Journal of Organic Chemistry
Copyright © 2021 Wiley-VCH GmbH. This work has been made available online in accordance with publisher policies or with permission. Permission for further reuse of this content should be sought from the publisher or the rights holder. This is the author created accepted manuscript following peer review and may differ slightly from the final published version. The final published version of this work is available at https://doi.org/10.1002/ejoc.202001670.
DescriptionM.M. thanks SULSA for a PhD studentship. We gratefully acknowledge financial support from the EPSRC (grant EP/I034793/1).
Items in the St Andrews Research Repository are protected by copyright, with all rights reserved, unless otherwise indicated.