The effect of the [18F]-PEG group on tracer qualification of [4-(phenylamino)-quinazoline-6-YL]-amide moiety--an EGFR putative irreversible inhibitor.
Previous reports have designated the labeled derivatives of [4-(phenylamino)-quinazoline-6-yl]-amide group as the most promising EGFR-PET imaging agent candidates. To further improve tracer qualifications and increase stability and solubility, additional derivatives of this group substituted at the 7-position with various lengths of fluoro-polyethyleneglycol (F-PEG) chains were synthesized. These novel derivatives inhibited EGFR autophosphorylation with IC(50) values of 5-40 nM. The compounds were successfully labeled with fluorine-18 at the PEG chain via a three-step radiosynthesis route. The labeled final products were obtained with a 13-32% decay corrected radiochemical yield, 99% radiochemical purity, and high specific activity.
Dissoki
Samar
S
Department of Medical Biophysics and Nuclear Medicine, Hadassah Hebrew University, Hadassah University Hospital, POB 12000, Jerusalem 91120, Israel.
Aviv
Yoel
Y
Laky
Desideriu
D
Abourbeh
Galith
G
Levitzki
Alexander
A
Mishani
Eyal
E
D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000737:chemistry*; D005462:Fluorine Radioisotopes; D010766:Phosphorylation; D011092:Polyethylene Glycols / Q000138:chemical synthesis* / Q000494:pharmacology; D011799:Quinazolines / Q000138:chemical synthesis* / Q000494:pharmacology; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000494:pharmacology
D005462:Fluorine Radioisotopes; D011799:Quinazolines; D019275:Radiopharmaceuticals; D011092:Polyethylene Glycols; D066246:ErbB Receptors