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Updated: Jun 19, 2026
A Combined 3D Tissue Engineered In Vitro/In Silico Lung Tumor Model for Predicting Drug Effectiveness in Specific Mutational Backgrounds
Published on: April 6, 2016
Molecular imaging of gefitinib activity in an epidermal growth factor receptor (EGFR)-bearing xenograft model
Jing Gong1, David J Yang, Saady Kohanim
1Department of Investigational Cancer Therapeutics (Phase I Program), Division of Cancer Medicine, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
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.
Insights
This study introduces a novel imaging agent, indium-labeled anti-phospho-tyrosine antibody ((111)In-EC-P-Tyr), to detect tumor phosphokinase activity. The agent successfully identified differences in kinase activity in animal models, showing potential for predicting patient response to targeted therapies.
Area of Science:
- Oncology
- Radiochemistry
- Molecular Imaging
Background:
- Identifying patients likely to respond to targeted cancer therapies is crucial.
- Noninvasive methods are needed to assess tumor-specific molecular targets.
- Phospho-tyrosine kinase activity is a key indicator in many cancers.
Purpose of the Study:
- To develop and evaluate an imaging agent for detecting tumor phosphokinase activity.
- To assess the potential of (111)In-EC-P-Tyr to predict response to kinase inhibitors.
- To validate the agent in preclinical cancer models.
Main Methods:
- An anti-phospho-tyrosine antibody was labeled with indium-111 using ethylenedicysteine (EC).
- The resulting agent, (111)In-EC-P-Tyr, was tested in A431 xenografts (EGFR-overexpressing).
- Biodistribution and imaging studies were performed before and after gefitinib treatment.
Main Results:
- Increased tumor-to-muscle ratios of (111)In-EC-P-Tyr were observed in A431 models.
- A significant decrease in tumor uptake of (111)In-EC-P-Tyr was noted in gefitinib-sensitive A431 cells after treatment.
- (111)In-EC-P-Tyr uptake remained high in gefitinib-resistant H441 cells.
Conclusions:
- (111)In-EC-P-Tyr can effectively detect tumor phospho-tyrosine kinase activity in preclinical models.
- This imaging agent shows promise for predicting patient response to kinase inhibitor therapies.
- Further clinical investigation is warranted to confirm its utility in patient selection.
