Dual-modality micro-positron emission tomography/computed tomography and near-infrared fluorescence imaging of EphB4 in orthotopic glioblastoma xenograft models.

Abstract

PURPOSE:

In glioblastoma, EphB4 receptors, a member of the largest family of receptor tyrosine kinases, are overexpressed in both tumor cells and angiogenic blood vessels. The purpose of this study was to examine whether the EphB4-binding peptide TNYL-RAW labeled with both (64)Cu and near-infrared fluorescence dye Cy5.5 could be used as a molecular imaging agent for dual-modality positron emission tomography/computed tomography [PET/CT] and optical imaging of human glioblastoma in orthotopic brain tumor models.

MATERIALS AND METHODS:

TNYL-RAW was conjugated to Cy5.5 and the radiometal chelator 1,4,7,10-tetraazadodecane-N,N',N″,N‴-tetraacetic acid. The conjugate was then labeled with (64)Cu for in vitro binding and in vivo dual μPET/CT and optical imaging studies in nude mice implanted with EphB4-expressing U251 and EphB4-negative U87 human glioblastoma cells. Tumors and brains were removed at the end of the imaging sessions for immunohistochemical staining and fluorescence microscopic examinations.

RESULTS:

μPET/CT and near-infrared optical imaging clearly showed specific uptake of the dual-labeled TNYL-RAW peptide in both U251 and U87 tumors in the brains of the nude mice after intravenous injection of the peptide. In U251 tumors, the Cy5.5-labeled peptide colocalized with both tumor blood vessels and tumor cells; in U87 tumors, the tracer colocalized only with tumor blood vessels, not with tumor cells.

CONCLUSIONS:

Dual-labeled EphB4-specific peptide could be used as a noninvasive molecular imaging agent for PET/CT and optical imaging of glioblastoma owing to its ability to bind to both EphB4-expressing angiogenic blood vessels and EphB4-expressing tumor cells.

• Authors: Miao Huang, Chiyi Xiong, Wei Lu, Rui Zhang, Min Zhou, Qian Huang, Jeffrey Weinberg, Chun Li
• Journal: Molecular imaging and biology (Mol Imaging Biol) Vol. 16 Issue 1 Pg. 74-84 (Feb 2014) ISSN: 1860-2002 [Electronic] United States
• PMID: 23918654 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• CY5.5 cyanine dye
• Carbocyanines
• Heterocyclic Compounds, 1-Ring
• Peptides
• TNYL-RAW peptide
• 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
• Luciferases
• Receptor, EphB4

Topics

• Animals
• Autoradiography
• Brain Neoplasms (diagnostic imaging, pathology)
• Carbocyanines (metabolism)
• Cell Line, Tumor
• Fluorescence
• Fluorescent Antibody Technique
• Glioblastoma (diagnostic imaging, pathology)
• Heterocyclic Compounds, 1-Ring
• Humans
• Infrared Rays
• Kinetics
• Luciferases (metabolism)
• Male
• Mice
• Mice, Nude
• Peptides
• Positron-Emission Tomography
• Receptor, EphB4 (metabolism)
• Surface Plasmon Resonance
• Tissue Distribution
• Tomography, X-Ray Computed
• Xenograft Model Antitumor Assays