A boronate-caged [¹⁸F]FLT probe for hydrogen peroxide detection using positron emission tomography

J Am Chem Soc. 2014 Oct 22;136(42):14742-5. doi: 10.1021/ja509198w. Epub 2014 Oct 13.

Abstract

Reactive oxygen species (ROS) play important roles in the development and progression of cancer and other diseases, motivating the development of translatable technologies for biological ROS imaging. Here we report Peroxy-Caged-[(18)F]Fluorodeoxy thymidine-1 (PC-FLT-1), an oxidatively immolative positron emission tomography (PET) probe for H2O2 detection. PC-FLT-1 reacts with H2O2 to generate [(18)F]FLT, allowing its peroxide-dependent uptake and retention in proliferating cells. The relative uptake of PC-FLT-1 was evaluated using H2O2-treated UOK262 renal carcinoma cells and a paraquat-induced oxidative stress cell model, demonstrating ROS-dependent tracer accumulation. The data suggest that PC-FLT-1 possesses promising characteristics for translatable ROS detection and provide a general approach to PET imaging that can be expanded to the in vivo study of other biologically relevant analytes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Transport
  • Boronic Acids / chemistry*
  • Cell Line, Tumor
  • Dideoxynucleosides / chemistry*
  • Dideoxynucleosides / metabolism
  • Humans
  • Hydrogen Peroxide / analysis*
  • Hydrogen Peroxide / metabolism
  • Hydrogen Peroxide / pharmacology
  • Positron-Emission Tomography*

Substances

  • Boronic Acids
  • Dideoxynucleosides
  • Hydrogen Peroxide
  • alovudine