A fully automated two-step synthesis of an (18)F-labelled tyrosine kinase inhibitor for EGFR kinase activity imaging in tumors.

Abstract

Radiolabelled epidermal growth factor receptor (EGFR) tyrosine kinase (TK) inhibitors potentially facilitate the assessment of EGFR overexpression in tumors. Since elaborate multi-step radiosyntheses are required for (18)F-labelling of EGFR-specific anilinoquinazolines we report on the development of a two-step click labelling approach that was adapted to a fully automated synthesis module. 6-(4-N,N-Dimethylaminocrotonyl)amido-4-(3-chloro-4-fluoro)phenylamino-7-{3-[4-(2-[(18)F]fluoroethyl)-2,3,4-triazol-1-yl]propoxy}quinazoline ([(18)F]6) was synthesized via Huisgen 1,3-dipolar cycloaddition between 2-[(18)F]fluoroethylazide ([(18)F]4) and the alkyne modified anilinoquinazoline precursor 5. PET images of PC9 tumor xenograft using the novel biomarker showed promising results to visualize EGFR overexpression.

• Authors: D Kobus, Y Giesen, R Ullrich, H Backes, B Neumaier
• Journal: Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine (Appl Radiat Isot) Vol. 67 Issue 11 Pg. 1977-84 (Nov 2009) ISSN: 1872-9800 [Electronic] England
• PMID: 19695886 (Publication Type: Journal Article)

Chemical References

• Fluorine Radioisotopes
• Radiopharmaceuticals
• EGFR protein, mouse
• ErbB Receptors
• Protein-Tyrosine Kinases

Topics

• Adenocarcinoma (diagnostic imaging, enzymology)
• Animals
• Cell Line, Tumor
• ErbB Receptors (metabolism)
• Fluorine Radioisotopes (chemistry, pharmacokinetics)
• Humans
• Isotope Labeling (methods)
• Metabolic Clearance Rate
• Mice
• Organ Specificity
• Protein-Tyrosine Kinases (antagonists & inhibitors)
• Radionuclide Imaging
• Radiopharmaceuticals (chemical synthesis, pharmacokinetics)
• Tissue Distribution