Synthesis, radiosynthesis and in vitro studies on novel hypoxia PET tracers incorporating [18F]FDR

Matteo Zanda, Manuele Musolino, Ian N. Fleming, Lutz F. Schweiger, David O’Hagan, Sergio Dall’Angelo

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

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 (15 ac), 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.
Original languageEnglish
JournalEuropean Journal of Organic Chemistry
VolumeEarly View
Early online date22 Feb 2021
DOIs
Publication statusE-pub ahead of print - 22 Feb 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