Pretargeted PET Imaging Using a Bioorthogonal 18F-Labeled trans-Cyclooctene in an Ovarian Carcinoma Model

Bioconjug Chem. 2017 Dec 20;28(12):2915-2920. doi: 10.1021/acs.bioconjchem.7b00635. Epub 2017 Dec 11.

Abstract

In cancer research, pretargeted positron emission tomography (PET) imaging has emerged as an effective two-step approach that combines the excellent target affinity and selectivity of antibodies with the advantages of using short-lived radionuclides such as fluorine-18. One possible approach is based on the bioorthogonal inverse-electron-demand Diels-Alder (IEDDA) reaction between tetrazines and trans-cyclooctene (TCO) derivatives. Here, we report the first successful use of an 18F-labeled small TCO compound, [18F]1 recently developed in our laboratory, to perform pretargeted immuno-PET imaging. The study was performed in an ovarian carcinoma mouse model, using a trastuzumab-tetrazine conjugate.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cycloaddition Reaction
  • Cyclooctanes / chemistry*
  • Female
  • Fluorine Radioisotopes*
  • Humans
  • Immunoconjugates / chemistry
  • Immunoconjugates / pharmacokinetics
  • Isotope Labeling
  • Mice
  • Ovarian Neoplasms / diagnostic imaging
  • Ovarian Neoplasms / pathology*
  • Positron-Emission Tomography / methods*
  • Tissue Distribution

Substances

  • Cyclooctanes
  • Fluorine Radioisotopes
  • Immunoconjugates
  • Fluorine-18