Design, Synthesis, and Evaluation of a Low-Molecular-Weight (11)C-Labeled Tetrazine for Pretargeted PET Imaging Applying Bioorthogonal in Vivo Click Chemistry

Bioconjug Chem. 2016 Jul 20;27(7):1707-12. doi: 10.1021/acs.bioconjchem.6b00234. Epub 2016 Jul 1.

Abstract

A low-molecular-weight tetrazine labeled with the short-lived positron emitter carbon-11 was developed as a bioorthogonal PET probe for pretargeted imaging. A method for efficient and fast synthesis of this imaging agent is presented using radiolabeling of a readily available precursor. High reactivity with trans-cyclooctenes was observed and in vivo investigations including PET/MR scanning showed homogeneous biodistribution, good metabolic stability, and rapid excretion in naive mice. These properties are key to the success of bioorthogonal (11)C-PET imaging, which has been shown in a simple pretargeting experiment using TCO-modified mesoporous silica nanoparticles. Overall, this (11)C-labeled tetrazine represents a highly versatile and advantageous chemical tool for bioorthogonal PET imaging and enables pretargeting approaches using carbon-11 for the first time.

MeSH terms

  • Animals
  • Carbon Radioisotopes*
  • Chemistry Techniques, Synthetic
  • Click Chemistry
  • Drug Design*
  • Female
  • Isotope Labeling
  • Mice
  • Molecular Weight
  • Positron-Emission Tomography / methods*
  • Tetrazoles / chemical synthesis*
  • Tetrazoles / chemistry*
  • Tetrazoles / metabolism
  • Tetrazoles / pharmacokinetics
  • Tissue Distribution

Substances

  • Carbon Radioisotopes
  • Tetrazoles