Synthesis and evaluation of (18)F-labeled 4-nitrobenzyl derivatives for imaging tumor hypoxia with positron emission tomography: Comparison of 2-[(18)F]fluoroethyl carbonate and 2-[(18)F]fluoroethyl carbamate

Bioorg Med Chem Lett. 2016 Jan 15;26(2):584-588. doi: 10.1016/j.bmcl.2015.11.066. Epub 2015 Nov 19.

Abstract

Two 4-nitrobenzyl derivatives, 2-fluoroethyl 4-nitrobenzyl carbonate 1 and 4-nitrobenzyl N-2-fluoroethyl carbamate 2, were radiolabeled with (18)F and evaluated for imaging tumor hypoxia with positron emission tomography. Although good tumor uptake was observed for [(18)F]1 and [(18)F]2 (>2.5%ID/g at 3-h post-injection), the tracers cleared slowly from nontarget tissues (>1.5%ID/g) and exhibited extensive defluorination in vivo (>4.0%ID/g for bone). Therefore, [(18)F]1 and [(18)F]2 are not suitable for imaging tumor hypoxia due to suboptimal tumor-to-background contrasts.

Keywords: 2-Fluoroethanol; 2-Fluoroethylamine; Fluorine-18; Hypoxia; Nitroreductase; Positron emission tomography.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbamates / chemistry*
  • Carbamates / pharmacokinetics
  • Carbonates / chemistry*
  • Carbonates / pharmacokinetics
  • Cell Line, Tumor
  • Colon / diagnostic imaging
  • Colonic Neoplasms / complications
  • Colonic Neoplasms / diagnostic imaging*
  • Fluorine Radioisotopes / chemistry*
  • Fluorine Radioisotopes / pharmacokinetics
  • Humans
  • Hypoxia / complications
  • Hypoxia / diagnostic imaging*
  • Mice
  • Mice, SCID
  • Nitrobenzenes / chemistry*
  • Nitrobenzenes / pharmacokinetics
  • Positron-Emission Tomography / methods*

Substances

  • Carbamates
  • Carbonates
  • Fluorine Radioisotopes
  • Nitrobenzenes