title: Dual-modality micro-positron emission tomography/computed tomography and near-infrared fluorescence imaging of EphB4 in orthotopic glioblastoma xenograft models.
abstract: OBJECTIVE
  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.
  
  
  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.affiliation: Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Unit 59, 1515 Holcombe Boulevard, Houston, TX, 77030, USA.
authors.forename: Miao
authors.initials: M
authors.lastname: Huang
authors.forename: Chiyi
authors.initials: C
authors.lastname: Xiong
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.forename: Min
authors.initials: M
authors.lastname: Zhou
authors.forename: Qian
authors.initials: Q
authors.lastname: Huang
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Weinberg
authors.forename: Chun
authors.initials: C
authors.lastname: Li
mesh_terms: D000818:Animals; D001345:Autoradiography; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D002232:Carbocyanines / Q000378:metabolism; D045744:Cell Line, Tumor; D005453:Fluorescence; D005455:Fluorescent Antibody Technique; D005909:Glioblastoma / Q000000981:diagnostic imaging* / Q000473:pathology; D006573:Heterocyclic Compounds, 1-Ring; D006801:Humans; D007259:Infrared Rays; D007700:Kinetics; D008156:Luciferases / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010455:Peptides; D049268:Positron-Emission Tomography; D036224:Receptor, EphB4 / Q000378:metabolism*; D020349:Surface Plasmon Resonance; D014018:Tissue Distribution; D014057:Tomography, X-Ray Computed; D023041:Xenograft Model Antitumor Assays
chemical_list: C098793:CY5.5 cyanine dye; D002232:Carbocyanines; D006573:Heterocyclic Compounds, 1-Ring; D010455:Peptides; C509441:TNYL-RAW peptide; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; D008156:Luciferases; D036224:Receptor, EphB4
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