title: A Cy5.5-labeled phage-displayed peptide probe for near-infrared fluorescence imaging of tumor vasculature in living mice.
abstract: Near-infrared (NIR) fluorescence optical imaging is an emerging imaging technique for studying diseases at the molecular level. Optical imaging with a NIR emitting fluorophore for targeting tumor vasculature offers a noninvasive method for early detection of tumor angiogenesis and efficient monitoring of response to anti-tumor vasculature therapy. The previous in vitro results demonstrated that the GX1 peptide, identified by phage-display technology, is a tumor vasculature endothelium-specific ligand. In this report, Cy5.5-conjugated GX1 peptide was evaluated in a subcutaneous U87MG glioblastoma xenograft model to investigate tumor-targeting efficacy. The in vitro flow cytometry results revealed dose-dependent binding of Cy5.5-GX1 peptide to U87MG glioma cells. In vivo optical imaging with the Cy5.5-GX1 probe exhibited rapid U87MG tumor targeting at 0.5 h p.i., and high tumor-to-background contrast at 4 h p.i. Tumor specificity of Cy5.5-GX1 was confirmed by effective blocking of tumor uptake in the presence of unlabeled GX1 peptide (20 mg/kg). Ex vivo imaging further confirmed in vivo imaging findings, and demonstrated that Cy5.5-GX1 has a tumor-to-muscle ratio (15.21 ± 0.84) at 24 h p.i. for the non-blocked group and significantly decreased ratio (6.95 ± 0.75) for the blocked group. In conclusion, our studies suggest that Cy5.5-GX1 is a promising molecular probe for optical imaging of tumor vasculature.
authors.affiliation: Molecular Imaging Center, Department of Radiology, Keck School of Medicine, University of Southern California, 2250 Alcazar Street, CSC 103, Los Angeles, CA 90033-9061, USA. chenkai@usc.edu
authors.forename: Kai
authors.initials: K
authors.lastname: Chen
authors.forename: Li-Peng
authors.initials: LP
authors.lastname: Yap
authors.forename: Ryan
authors.initials: R
authors.lastname: Park
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Hui
authors.forename: Kaichun
authors.initials: K
authors.lastname: Wu
authors.forename: Daiming
authors.initials: D
authors.lastname: Fan
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Chen
authors.forename: Peter S
authors.initials: PS
authors.lastname: Conti
mesh_terms: D000818:Animals; D001435:Bacteriophages / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002232:Carbocyanines / Q000737:chemistry; D045744:Cell Line, Tumor; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D057054:Molecular Imaging / Q000295:instrumentation / Q000379:methods*; D015335:Molecular Probes / Q000737:chemistry / Q000235:genetics; D009389:Neovascularization, Pathologic; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry / Q000235:genetics; D013050:Spectrometry, Fluorescence / Q000379:methods; D019265:Spectroscopy, Near-Infrared / Q000379:methods; D013270:Stomach / Q000098:blood supply / Q000737:chemistry; D013274:Stomach Neoplasms / Q000737:chemistry / Q000175:diagnosis*
chemical_list: C098793:CY5.5 cyanine dye; D002232:Carbocyanines; D005456:Fluorescent Dyes; D015335:Molecular Probes; D019151:Peptide Library; D010455:Peptides