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.