TY - JOUR
T1 - Dual-modality micro-positron emission tomography/computed tomography and near-infrared fluorescence imaging of EphB4 in orthotopic glioblastoma xenograft models
AU - Huang, Miao
AU - Xiong, Chiyi
AU - Lu, Wei
AU - Zhang, Rui
AU - Zhou, Min
AU - Huang, Qian
AU - Weinberg, Jeffrey
AU - Li, Chun
N1 - Funding Information:
Acknowledgments. We thank Erica Goodoff for editing the manuscript. This work was supported in part by the John S. Dunn Foundation. The small animal imaging facility of the University of Texas MD Anderson Cancer Center is supported in part by the National Institutes of Health through MD Anderson Cancer Center Support Grant CA016672.
PY - 2014/2
Y1 - 2014/2
N2 - 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 64Cu 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″,Nâ€́- tetraacetic acid. The conjugate was then labeled with 64Cu 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.
AB - 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 64Cu 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″,Nâ€́- tetraacetic acid. The conjugate was then labeled with 64Cu 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.
KW - EphB4
KW - Near-infrared
KW - Optical imaging
KW - Peptide
KW - μPET/CT
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U2 - 10.1007/s11307-013-0674-3
DO - 10.1007/s11307-013-0674-3
M3 - Article
C2 - 23918654
AN - SCOPUS:84895077478
SN - 1536-1632
VL - 16
SP - 74
EP - 84
JO - Molecular Imaging and Biology
JF - Molecular Imaging and Biology
IS - 1
ER -