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

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.