title: Radiosynthesis of ML03, a novel positron emission tomography biomarker for targeting epidermal growth factor receptor via the labeling synthon: [11C]acryloyl chloride.
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.
authors.affiliation: Department of Medical Biophysics and Nuclear Medicine, Hadassah Hebrew University Hospital, Jerusalem, Israel.
authors.forename: Iris
authors.initials: I
authors.lastname: Ben-David
authors.forename: Yulia
authors.initials: Y
authors.lastname: Rozen
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Ortu
authors.forename: Eyal
authors.initials: E
authors.lastname: Mishani
mesh_terms: D000178:Acrylamides / Q000138:chemical synthesis* / Q000627:therapeutic use; D000179:Acrylates; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000627:therapeutic use; D002250:Carbon Radioisotopes; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D020128:Inhibitory Concentration 50; D010766:Phosphorylation / Q000187:drug effects; D011799:Quinazolines / Q000138:chemical synthesis* / Q000627:therapeutic use; D019275:Radiopharmaceuticals / Q000138:chemical synthesis*; D014055:Tomography, Emission-Computed / Q000379:methods; D014407:Tumor Cells, Cultured
chemical_list: D000178:Acrylamides; D000179:Acrylates; D000970:Antineoplastic Agents; D002250:Carbon Radioisotopes; C465666:N-(4-((4,5-dichloro-2-fluorophenyl)amino)quinazolin-6-yl)acrylamide; D011799:Quinazolines; D019275:Radiopharmaceuticals; C026200:acryloyl chloride; D066246:ErbB Receptors