Development of a new epidermal growth factor receptor positron emission tomography imaging agent based on the 3-cyanoquinoline core: Synthesis and biological evaluation

Federica Pisaneschi, Quang De Nguyen, Elham Shamsaei, Matthias Glaser, Edward Robins, MacIej Kaliszczak, Graham Smith, Alan C. Spivey, Eric O. Aboagye

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51 Citations (Scopus)


The epidermal growth factor receptor (EGFR/c-ErbB1/HER1) is overexpressed in many cancers including breast, ovarian, endometrial, and non-small cell lung cancer. An EGFR specific imaging agent could facilitate clinical evaluation of primary tumors and/or metastases. To achieve this goal we designed and synthesized a small array of fluorine containing compounds based on a 3-cyanoquinoline core. A lead compound, 16, incorporating 2′-fluoroethyl- 1,2,3-triazole was selected for evaluation as a radioligand based on its high affinity for EGFR kinase (IC50 = 1.81 ± 0.18 nM), good cellular potency (IC50 = 21.97 ± 9.06 nM), low lipophilicity and good metabolic stability. 'Click' labeling afforded [18F]16 in 37.0 ± 3.6% decay corrected radiochemical yield based on azide [ 18F]14 and 7% end of synthesis (EOS) yield from aqueous fluoride. Compound [18F]16 was obtained with >99% radiochemical purity in a total synthesis time of 3 h. The compound showed good stability in vivo and a fourfold higher uptake in high EGFR expressing A431 tumor xenografts compared to low EGFR expressing HCT116 tumor xenografts. Furthermore, the radiotracer could be visualized in A431 tumor bearing mice by small animal PET imaging. Compound [18F]16 therefore constitutes a promising radiotracer for further evaluation for imaging of EGFR status.

Original languageEnglish
Pages (from-to)6634-6645
Number of pages12
JournalBioorganic and Medicinal Chemistry
Issue number18
Publication statusPublished or Issued - 15 Sept 2010
Externally publishedYes


  • 3-Cyanoquinoline
  • [F]-PET imaging
  • Click chemistry
  • EGFR

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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