Identifying nonsmall-cell lung tumours bearing the T790M EGFR TKI resistance mutation using PET imaging

J Labelled Comp Radiopharm. 2019 Jul;62(9):596-603. doi: 10.1002/jlcr.3771. Epub 2019 Jul 16.

Abstract

Specific mutations significantly affect response to epidermal growth factor tyrosine kinase inhibitor (EGFR-TKI) treatment in lung cancer patients. Identifying patients with these mutations remains a major clinical challenge. EGFR T790M mutation, which conveys resistance to in the present study, [18 F]FEWZ was assessed in vitro to determine efficacy relative to the starting compound and in vivo to measure the biodistribution and specificity of binding to EGFR wild-type, L858R and T790M bearing tumours. [18 F]FEWZ is the first evidence of a radiolabeled third generation anilinopyrimidine-derived tyrosine kinase inhibitor targeting T790M mutation bearing tumours in vivo.

Keywords: epidermal growth factor receptor (EGFR); mutation; nonsmall-cell lung cancer (NSCLC); resistance; tyrosine kinase inhibitor (TKI).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Non-Small-Cell Lung / diagnostic imaging*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic
  • Drug Resistance, Neoplasm / genetics*
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / genetics*
  • Isotope Labeling
  • Lung Neoplasms / diagnostic imaging*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Male
  • Mice
  • Mutation*
  • Positron-Emission Tomography*
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacokinetics
  • Protein Kinase Inhibitors / pharmacology*
  • Pyrimidines / chemistry
  • Pyrimidines / pharmacokinetics
  • Pyrimidines / pharmacology
  • Tissue Distribution

Substances

  • Protein Kinase Inhibitors
  • Pyrimidines
  • ErbB Receptors
  • pyrimidine