Potential (18)F-labeled biomarkers for epidermal growth factor receptor tyrosine kinase.
As PET candidate tracers for EGFr-TK, five 4-(anilino)quinazoline derivatives, 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 (18)F and cell binding experiments, biodistribution and PET studies in A431 tumor-bearing mice were performed. 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 clearance make them unsuitable as tracers for nuclear medicine imaging of EGFr-TK.
Bonasera
T A
TA
Hebrew University, Hadassah University Hospital Campus, Department of Medical Biophysics and Nuclear Medicine, IL-91120, Jerusalem, Israel.
Ortu
G
G
Rozen
Y
Y
Krais
R
R
Freedman
N M
NM
Chisin
R
R
Gazit
A
A
Levitzki
A
A
Mishani
E
E
D000818:Animals; D002455:Cell Division; D002851:Chromatography, High Pressure Liquid; D004797:Enzyme-Linked Immunosorbent Assay; D066246:ErbB Receptors / Q000378:metabolism*; D005462:Fluorine Radioisotopes; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D010766:Phosphorylation; D011799:Quinazolines; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
D005462:Fluorine Radioisotopes; D011799:Quinazolines; D019275:Radiopharmaceuticals; D066246:ErbB Receptors