Title

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

UMMS Affiliation

Department of Radiology

Date

12-2013

Document Type

Article

Medical Subject Headings

Animals; Antibodies, Monoclonal; Brain Neoplasms; Cell Line, Tumor; Glioma; Humans; Magnetic Resonance Imaging; Molecular Imaging; Mutation; Rats; Rats, Nude; Receptor, Epidermal Growth Factor

Disciplines

Investigative Techniques | Neoplasms | Radiology | Therapeutics

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.

Rights and Permissions

Citation: Mol Imaging Biol. 2013 Dec;15(6):675-84. doi: 10.1007/s11307-013-0653-8. Link to article on publisher's site

Related Resources

Link to Article in PubMed

PubMed ID

23733229