Abstract |
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.
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Authors | Jing Gong, David J Yang, Saady Kohanim, Laura S Angelo, Razelle Kurzrock |
Journal | Cancer biology & therapy
(Cancer Biol Ther)
Vol. 8
Issue 23
Pg. 2239-47
(Dec 2009)
ISSN: 1555-8576 [Electronic] United States |
PMID | 19823028
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Indium Radioisotopes
- Protein Kinase Inhibitors
- Quinazolines
- ethylene dicysteine
- Technetium
- EGFR protein, mouse
- ErbB Receptors
- Cysteine
- Gefitinib
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Topics |
- Animals
- Apoptosis
(drug effects)
- Blotting, Western
- Cell Line, Tumor
- Cysteine
(analogs & derivatives, pharmacology)
- ErbB Receptors
(antagonists & inhibitors, metabolism)
- Female
- Flow Cytometry
- Gefitinib
- Humans
- Immunoprecipitation
- Indium Radioisotopes
- Mice
- Mice, Nude
- Molecular Imaging
- Neoplasms, Glandular and Epithelial
(diagnostic imaging, drug therapy, pathology)
- Phosphorylation
(drug effects)
- Protein Kinase Inhibitors
(pharmacology)
- Quinazolines
(pharmacology)
- Radionuclide Imaging
- Technetium
(pharmacology)
- Tissue Distribution
(drug effects)
- Xenograft Model Antitumor Assays
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