Format

Send to

Choose Destination
Bioorg Med Chem. 2010 Sep 15;18(18):6634-45. doi: 10.1016/j.bmc.2010.08.004. Epub 2010 Aug 6.

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

Author information

1
Comprehensive Cancer Imaging Centre, Department of Chemistry, Imperial College London, Faculty of Medicine, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, United Kingdom. f.pisaneschi@imperial.ac.uk

Abstract

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.

PMID:
20797871
DOI:
10.1016/j.bmc.2010.08.004
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science Icon for Spiral, Imperial College Digital Repository
Loading ...
Support Center