Molecular imaging of gefitinib activity in an epidermal growth factor receptor (EGFR)-bearing xenograft model

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 (¹¹¹In) using ethylenedicysteine (EC) as a chelator (¹¹¹In-EC-P-Tyr).  We hypothesized that tumor phosphokinase activity would be discernible by imaging with ¹¹¹In-EC-P-Tyr.  A xenograft of A431 cells, a human epithelial carcinoma cell line over-expressing epidermal growth factor receptor (EGFR), was employed.  Biodistribution studies confirmed increased tumor/muscle ratios of ¹¹¹In-EC-P-Tyr in the A431 model. Imaging demonstrated that a marked decrease in tumor uptake of ¹¹¹In-EC-P-Tyr occurred after three days of gefitinib therapy in A431 cells (gefitinib-sensitive), but not in H441 cells (gefitinb-resistant). Our results indicate that ¹¹¹In-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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