Influence of farnesyl transferase inhibitor treatment on epidermal growth factor receptor status.
The radiolabelled growth factor [(123/125)I] I-hEGF is evaluated in vitro and in vivo to monitor the acute effects on the EGFR of R115777, a farnesyl transferase inhibitor (FTI). Upregulation of the EGFR after incubation with R115777 correlated linearly with FTI induced acute growth inhibition. Receptor mediated [125I] I-hEGF internalization decreased following R115777 treatment. Preliminary data suggest that the net in vivo effect is a decrease of [123I] I-hEGF uptake in the tumour. These findings suggest the possible use of radioiodinated hEGF as a radiodiagnosticum to investigate EGFR status changes as a predictor for eventual FTI chemotherapy outcome in vivo.
Cornelissen
Bart
B
Laboratory of Radiopharmacy, Ghent University, Harelbekestraat 72, B-9000 Gent, Belgium. bart.cornelissen@ugent.be
Thonissen
Thomas
T
Kersemans
Veerle
V
Van De Wiele
Christophe
C
Lahorte
Christophe
C
Dierckx
Rudi A
RA
Slegers
Guido
G
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D000818:Animals; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004815:Epidermal Growth Factor / Q000737:chemistry / Q000378:metabolism; D066246:ErbB Receptors / Q000187:drug effects*; D051231:Farnesyltranstransferase; D006801:Humans; D007457:Iodine Radioisotopes / Q000737:chemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D015363:Quinolones / Q000494:pharmacology; D019275:Radiopharmaceuticals / Q000138:chemical synthesis; D012044:Regression Analysis; D014018:Tissue Distribution
D004791:Enzyme Inhibitors; D007457:Iodine Radioisotopes; D015363:Quinolones; D019275:Radiopharmaceuticals; D004815:Epidermal Growth Factor; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase; D066246:ErbB Receptors; C402769:tipifarnib