Synthesis, Radiosynthesis and in vitro Studies on Novel Hypoxia PET Tracers Incorporating [18F]FDR

Manuele Musolino, Ian N Fleming, Lutz F. Schweiger, David O'hagan, Sergio Dall'Angelo* (Corresponding Author), University Aberdeen* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Abstract

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 (15a-c), a cyclopropyl ring (15d) and a 1,4-disubstituted-1,2,3-triazole (15e). Experiments in hypoxic cells showed that 15d 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 15d displays a logP = 0.38 and the most rigid spacer. A sixth radiotracer (15f), with a 2-H-imidazole replacing the 2-nitroimidazole moiety of 15d, was used to demonstrate that the cyclopropyl group does not play a meaningful role in the sensitivity towards hypoxia.
Original languageEnglish
Pages (from-to)1429-1439
Number of pages11
JournalEuropean Journal of Organic Chemistry
Volume2021
Issue number9
Early online date22 Feb 2021
DOIs
Publication statusPublished - 5 Mar 2021

Bibliographical note

Funding Information:
M.M. thanks SULSA for a PhD studentship. We gratefully acknowledge financial support from the EPSRC (grant EP/I034793/1).

Data Availability Statement

As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors.

Keywords

  • FDR
  • Hypoxia
  • Positron emission
  • Radiochemistry
  • Tomography

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