The effect of the [18F]-PEG group on tracer qualification of [4-(phenylamino)-quinazoline-6-YL]-amide moiety--an EGFR putative irreversible inhibitor

Appl Radiat Isot. 2007 Oct;65(10):1140-51. doi: 10.1016/j.apradiso.2007.04.014. Epub 2007 May 8.

Abstract

Previous reports have designated the labeled derivatives of [4-(phenylamino)-quinazoline-6-yl]-amide group as the most promising EGFR-PET imaging agent candidates. To further improve tracer qualifications and increase stability and solubility, additional derivatives of this group substituted at the 7-position with various lengths of fluoro-polyethyleneglycol (F-PEG) chains were synthesized. These novel derivatives inhibited EGFR autophosphorylation with IC(50) values of 5-40 nM. The compounds were successfully labeled with fluorine-18 at the PEG chain via a three-step radiosynthesis route. The labeled final products were obtained with a 13-32% decay corrected radiochemical yield, 99% radiochemical purity, and high specific activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / chemistry*
  • Fluorine Radioisotopes*
  • Phosphorylation
  • Polyethylene Glycols / chemical synthesis*
  • Polyethylene Glycols / pharmacology
  • Quinazolines / chemical synthesis*
  • Quinazolines / pharmacology
  • Radiopharmaceuticals / chemical synthesis*
  • Radiopharmaceuticals / pharmacology

Substances

  • Fluorine Radioisotopes
  • Quinazolines
  • Radiopharmaceuticals
  • Polyethylene Glycols
  • ErbB Receptors