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MR Signal Amplification for Imaging of the Mutant EGF Receptor in Orthotopic Human Glioma Model

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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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Acknowledgments

This work was supported by 5RO1AG034901-03 and 5R01EB000858 grants to AB. We are grateful to Jamie O’Callaghan and Dr. Shaokuan Zheng for assistance with several technical aspects of this work. We are grateful to Dr. Mary Mazzanti for editing the text.

Conflict of Interest

The authors declare that they have no conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Radiology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA, 01655, USA

    Mohammed Salman Shazeeb, Suresh Gupta & Alexei Bogdanov Jr.

  2. Department of Cell Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA, 01655, USA

    Alexei Bogdanov Jr.

Authors
  1. Mohammed Salman Shazeeb
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  2. Suresh Gupta
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  3. Alexei Bogdanov Jr.
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Correspondence to Alexei Bogdanov Jr..

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Shazeeb, M.S., Gupta, S. & Bogdanov, A. MR Signal Amplification for Imaging of the Mutant EGF Receptor in Orthotopic Human Glioma Model. Mol Imaging Biol 15, 675–684 (2013). https://doi.org/10.1007/s11307-013-0653-8

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