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, Matteo Zanda

Research output: Contribution to journalArticlepeer-review

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
JournalEuropean Journal of Organic Chemistry
Volume2021
Issue number9
Early online date22 Feb 2021
DOIs
Publication statusPublished - 5 Mar 2021

Keywords

  • FDR
  • Hypoxia
  • Positron emission
  • Radiochemistry
  • Tomography

Fingerprint

Dive into the research topics of 'Synthesis, Radiosynthesis and in vitro Studies on Novel Hypoxia PET Tracers Incorporating [18F]FDR'. Together they form a unique fingerprint.

Cite this