title: 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.affiliation: Max Planck Institute for Neurological Research with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Faculty of Medicine of the University of Cologne, Cologne, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Kobus
authors.forename: Y
authors.initials: Y
authors.lastname: Giesen
authors.forename: R
authors.initials: R
authors.lastname: Ullrich
authors.forename: H
authors.initials: H
authors.lastname: Backes
authors.forename: B
authors.initials: B
authors.lastname: Neumaier
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging / Q000201:enzymology*; D000818:Animals; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000378:metabolism*; D005462:Fluorine Radioisotopes / Q000737:chemistry* / Q000493:pharmacokinetics*; D006801:Humans; D007553:Isotope Labeling / Q000379:methods; D008657:Metabolic Clearance Rate; D051379:Mice; D009928:Organ Specificity; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; C541485:EGFR protein, mouse; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases