MR signal amplification for imaging of the mutant EGF receptor in orthotopic human glioma model.

PURPOSE: To investigate the potential of targeted MR signal amplification strategy for imaging of EGF receptor variant III (EGFRvIII) overexpression associated with the infiltrating margin of aggressive orthotopic brain tumors. PROCEDURES: F(ab')2 fragments of humanized anti-EGFRvIII monoclonal antibody (EMD72000) were linked to deglycosylated horseradish peroxidase (HRP) and glucose oxidase (GOX). Detection of the F(ab')2 conjugate pair colocalization in vivo was enabled by a subsequent IV injection of a low molecular weight paramagnetic substrate of HRP, diTyr-GdDTPA.
RESULTS: The delivery of the targeted fragments to the tumor was validated using SPECT/CT imaging of radiolabeled anti-EGFRvIII F(ab')2 conjugates. Further, by using 3 T MRI, we observed time-dependent differences in tumor signal intensity and signal retention at the endpoint depending on whether or not the animals were pre-injected with the anti-EGFRvIII F(ab')2 conjugates.
CONCLUSIONS: Imaging of EGFRvIII expression in vivo was enabled by consecutive administration of targeted F(ab')2 conjugates and a paramagnetic substrate resulting in a tumor-specific receptor detection with high specificity and resolution.