EphA2 as a Diagnostic Imaging Target in Glioblastoma: A Positron Emission Tomography/Magnetic Resonance Imaging Study

Puttick, Simon, Stringer, Brett W., Day, Bryan W., Bruce, Zara C., Ensbey, Kathleen S., Mardon, Karine, Cowin, Gary J., Thurecht, Kristofer J, Whittaker, Andrew K., Fay, Michael, Boyd, Andrew W. and Rose, Stephen (2015) EphA2 as a Diagnostic Imaging Target in Glioblastoma: A Positron Emission Tomography/Magnetic Resonance Imaging Study. Molecular Imaging, 14 6: 385-395. doi:10.2310/7290.2015.00008

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Author Puttick, Simon
Stringer, Brett W.
Day, Bryan W.
Bruce, Zara C.
Ensbey, Kathleen S.
Mardon, Karine
Cowin, Gary J.
Thurecht, Kristofer J
Whittaker, Andrew K.
Fay, Michael
Boyd, Andrew W.
Rose, Stephen
Title EphA2 as a Diagnostic Imaging Target in Glioblastoma: A Positron Emission Tomography/Magnetic Resonance Imaging Study
Journal name Molecular Imaging   Check publisher's open access policy
ISSN 1535-3508
1536-0121
Publication date 2015-07-22
Year available 2015
Sub-type Article (original research)
DOI 10.2310/7290.2015.00008
Open Access Status File (Publisher version)
Volume 14
Issue 6
Start page 385
End page 395
Total pages 11
Place of publication Hamilton, Ontario, Canada
Publisher Decker Intellectual Properties
Collection year 2016
Language eng
Formatted abstract
Noninvasive imaging is a critical technology for diagnosis, classification, and subsequent treatment planning for patients with glioblastoma. It has been shown that the EphA2 receptor tyrosine kinase (RTK) is overexpressed in a number of tumors, including glioblastoma. Expression levels of Eph RTKs have been linked to tumor progression, metastatic spread, and poor patient prognosis. As EphA2 is expressed at low levels in normal neural tissues, this protein represents an attractive imaging target for delineation of tumor infiltration, providing an improved platform for image-guided therapy. In this study, EphA2-4B3, a monoclonal antibody specific to human EphA2, was labeled with 64Cu through conjugation to the chelator 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA). The resulting complex was used as a positron emission tomography (PET) tracer for the acquisition of high-resolution longitudinal PET/magnetic resonance images. EphA2-4B3-NOTA-64Cu images were qualitatively and quantitatively compared to the current clinical standards of [18F]FDOPA and gadolinium (Gd) contrast–enhanced MRI. We show that EphA2-4B3-NOTA-64Cu effectively delineates tumor boundaries in three different mouse models of glioblastoma. Tumor to brain contrast is significantly higher in EphA2-4B3-NOTA-64Cu images than in [18F]FDOPA images and Gd contrast–enhanced MRI. Furthermore, we show that nonspecific uptake in the liver and spleen can be effectively blocked by a dose of nonspecific (isotype control) IgG.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

 
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