Radiosynthesis of ML03, a novel positron emission tomography biomarker for targeting epidermal growth factor receptor via the labeling synthon: [11C]acryloyl chloride

Appl Radiat Isot. 2003 Feb;58(2):209-17. doi: 10.1016/s0969-8043(02)00301-9.

Abstract

An automated procedure for the radiosynthesis of the labeling synthon [11C]acryloyl chloride was developed and applied for labeling several N-acryl amides with carbon-11. [11C]-6-acrylamido-4-(3,4-dichloro-6-fluoroanilino)quinazoline (ML03), a novel PET biomarker targeting the epidermal growth factor receptor tyrosine kinase (EGFr-TK) in cancer, was successfully prepared using this labeled synthon in a fully automated manner. Two other potential anticancer drugs were also labeled using the developed methodology. The potency of ML03 to inhibit autophosphorylation of EGFr-TK was evaluated by an ELISA assay indicating a low IC(50) of 0.037nM.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acrylamides / chemical synthesis*
  • Acrylamides / therapeutic use
  • Acrylates
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / therapeutic use
  • Carbon Radioisotopes*
  • ErbB Receptors / antagonists & inhibitors*
  • Humans
  • Inhibitory Concentration 50
  • Phosphorylation / drug effects
  • Quinazolines / chemical synthesis*
  • Quinazolines / therapeutic use
  • Radiopharmaceuticals / chemical synthesis*
  • Tomography, Emission-Computed / methods
  • Tumor Cells, Cultured

Substances

  • Acrylamides
  • Acrylates
  • Antineoplastic Agents
  • Carbon Radioisotopes
  • N-(4-((4,5-dichloro-2-fluorophenyl)amino)quinazolin-6-yl)acrylamide
  • Quinazolines
  • Radiopharmaceuticals
  • acryloyl chloride
  • ErbB Receptors