MR Signal Amplification for Imaging of the Mutant EGF Receptor in Orthotopic Human Glioma Model |
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| Authors: | Mohammed Salman Shazeeb Suresh Gupta Alexei Bogdanov Jr |
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| Institution: | 1. Department of Radiology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA, 01655, USA
2. Department of Cell Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA, 01655, USA
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| Abstract: | 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. |
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