Ortho-Stabilized (18) F-Azido Click Agents and their Application in PET Imaging with Single-Stranded DNA Aptamers

Angew Chem Int Ed Engl. 2015 Oct 19;54(43):12777-81. doi: 10.1002/anie.201505927. Epub 2015 Aug 20.

Abstract

Azido (18) F-arenes are important and versatile building blocks for the radiolabeling of biomolecules via Huisgen cycloaddition ("click chemistry") for positron emission tomography (PET). However, routine access to such clickable agents is challenged by inefficient and/or poorly defined multistep radiochemical approaches. A high-yielding direct radiofluorination for azido (18) F-arenes was achieved through the development of an ortho-oxygen-stabilized iodonium derivative (OID). This OID strategy addresses an unmet need for a reliable azido (18) F-arene clickable agent for bioconjugation reactions. A ssDNA aptamer was radiolabeled with this agent and visualized in a xenograft mouse model of human colon cancer by PET, which demonstrates that this OID approach is a convenient and highly efficient way of labeling and tracking biomolecules.

Keywords: PET imaging; aptamers; bioconjugation; fluorine; radiopharmaceuticals.

Publication types

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

MeSH terms

  • Animals
  • Aptamers, Nucleotide / chemistry*
  • Azides / chemistry
  • Cell Adhesion Molecules / analysis*
  • Click Chemistry
  • Colon / pathology*
  • Colonic Neoplasms / diagnosis*
  • DNA, Single-Stranded / chemistry*
  • Female
  • Fluorine Radioisotopes / chemistry
  • HCT116 Cells
  • Humans
  • Mice
  • Positron-Emission Tomography / methods*
  • Radiopharmaceuticals / chemistry
  • Receptor Protein-Tyrosine Kinases / analysis*

Substances

  • 18F-Tr-Sgc8
  • Aptamers, Nucleotide
  • Azides
  • Cell Adhesion Molecules
  • DNA, Single-Stranded
  • Fluorine Radioisotopes
  • Radiopharmaceuticals
  • PTK7 protein, human
  • Receptor Protein-Tyrosine Kinases