Molecular imaging of gefitinib activity in an epidermal growth factor receptor (EGFR)-bearing xenograft model. Cancer Biol Ther 2009 Dec;8(23):2239-47
Date
10/14/2009Pubmed ID
19823028DOI
10.4161/cbt.8.23.9986Scopus ID
2-s2.0-73949101989 (requires institutional sign-in at Scopus site) 2 CitationsAbstract
Finding noninvasive methods to discern which patients' tumors bear a specific target molecule, and are presumably more likely to respond, remains a critical challenge. An anti-phospho-tyrosine antibody was labeled with indium ((111)In) using ethylenedicysteine (EC) as a chelator ((111)In-EC-P-Tyr). We hypothesized that tumor phosphokinase activity would be discernible by imaging with (111)In-EC-P-Tyr. A xenograft of A431 cells, a human epithelial carcinoma cell line overexpressing epidermal growth factor receptor (EGFR), was employed. Biodistribution studies confirmed increased tumor/muscle ratios of (111)In-EC-P-Tyr in the A431 model. Imaging demonstrated that a marked decrease in tumor uptake of (111)In-EC-P-Tyr occurred after 3 d of gefitinib therapy in A431 cells (gefitinib-sensitive), but not in H441 cells (gefitinib-resistant). Our results indicate that (111)In-EC-P-Tyr can detect tumor phospho-tyrosine kinase activity in animal models. This type of agent merits investigation in the clinic to determine if it can predict patient responses to kinase inhibitors based on phosphokinase imaging.
Author List
Gong J, Yang DJ, Kohanim S, Angelo LS, Kurzrock RAuthor
Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsApoptosis
Blotting, Western
Cell Line, Tumor
Cysteine
ErbB Receptors
Female
Flow Cytometry
Humans
Immunoprecipitation
Indium Radioisotopes
Mice
Mice, Nude
Molecular Imaging
Neoplasms, Glandular and Epithelial
Phosphorylation
Protein Kinase Inhibitors
Quinazolines
Radionuclide Imaging
Technetium
Tissue Distribution
Xenograft Model Antitumor Assays