A fully automated two-step synthesis of an (18)F-labelled tyrosine kinase inhibitor for EGFR kinase activity imaging in tumors

Appl Radiat Isot. 2009 Nov;67(11):1977-84. doi: 10.1016/j.apradiso.2009.07.018. Epub 2009 Aug 3.

Abstract

Radiolabelled epidermal growth factor receptor (EGFR) tyrosine kinase (TK) inhibitors potentially facilitate the assessment of EGFR overexpression in tumors. Since elaborate multi-step radiosyntheses are required for (18)F-labelling of EGFR-specific anilinoquinazolines we report on the development of a two-step click labelling approach that was adapted to a fully automated synthesis module. 6-(4-N,N-Dimethylaminocrotonyl)amido-4-(3-chloro-4-fluoro)phenylamino-7-{3-[4-(2-[(18)F]fluoroethyl)-2,3,4-triazol-1-yl]propoxy}quinazoline ([(18)F]6) was synthesized via Huisgen 1,3-dipolar cycloaddition between 2-[(18)F]fluoroethylazide ([(18)F]4) and the alkyne modified anilinoquinazoline precursor 5. PET images of PC9 tumor xenograft using the novel biomarker showed promising results to visualize EGFR overexpression.

MeSH terms

  • Adenocarcinoma / diagnostic imaging
  • Adenocarcinoma / enzymology*
  • Animals
  • Cell Line, Tumor
  • ErbB Receptors / metabolism*
  • Fluorine Radioisotopes / chemistry*
  • Fluorine Radioisotopes / pharmacokinetics*
  • Humans
  • Isotope Labeling / methods
  • Metabolic Clearance Rate
  • Mice
  • Organ Specificity
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Radionuclide Imaging
  • Radiopharmaceuticals / chemical synthesis
  • Radiopharmaceuticals / pharmacokinetics
  • Tissue Distribution

Substances

  • Fluorine Radioisotopes
  • Radiopharmaceuticals
  • EGFR protein, mouse
  • ErbB Receptors
  • Protein-Tyrosine Kinases