Potential F-18-labeled biomarkers for epidermal growth factor receptor tyrosine kinase

As PET candidate tracers for EGFr-TK, five 4-(anilino)quinazoline derivativ es, each fluorinated in the aniline moiety, were prepared. Each was tested in vitro for inhibition of EGFr autophosphorylation in A431 cell line. The leading compounds were then radiolabeled with F-18 and cell binding experim ents, biodistribution and PET studies in A431 tumor-bearing mice were perfo rmed. Metabolic studies were carried out in a mice control group. From our results, we concluded that while in vitro experiments indicates efficacy of 4-(anilino)quinazoline compounds, kinetic factors and rapid blood clearanc e make them unsuitable as tracers for nuclear medicine imaging of EGFr-TK. (C) 2001 Elsevier Science Inc. All rights reserved.