In vivo imaging of tumor vascular endothelial cells

Dawen Zhao, Jason H. Stafford, Heling Zhou, Philip E. Thorpe

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

Phosphatidylserine (PS), normally restricted to the inner leaflet of the plasma membrane, becomes exposed on the outer surface of viable (non-apoptotic) endothelial cells in tumor blood vessels, probably in response to oxidative stresses present in the tumor microenvironment. In the present study, we optically imaged exposed PS on tumor vasculature in vivo using PGN635, a novel human monoclonal antibody that targets PS. PGN635 F(ab′)2 was labeled with the near infrared (NIR) dye, IRDye 800CW. Human glioma U87 cells or breast cancer MDA-MB-231 cells were implanted subcutaneously or orthotopically into nude mice. When the tumors reached ∼5 mm in diameter, 800CW- PGN635 was injected via a tail vein and in vivo dynamic NIR imaging was performed. For U87 gliomas, NIR imaging allowed clear detection of tumors as early as 4 h later, which improved over time to give a maximal tumor/normal ratio (TNR = 2.9 ± 0.5) 24 h later. Similar results were observed for orthotopic MDA-MB-231 breast tumors. Localization of 800CW-PGN635 to tumors was antigen specific since 800CW-Aurexis, a control probe of irrelevant specificity, did not localize to the tumors, and pre-administration of unlabeled PGN635 blocked the uptake of 800CW-PGN635. Fluorescence microscopy confirmed that 800CW-PGN635 was binding to PS-positive tumor vascular endothelium. Our studies suggest that tumor vasculature can be successfully imaged in vivo to provide sensitive tumor detection.

Original languageEnglish (US)
Title of host publicationReporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications V
DOIs
StatePublished - May 30 2013
EventReporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications V - San Francisco, CA, United States
Duration: Feb 4 2013Feb 6 2013

Publication series

NameProgress in Biomedical Optics and Imaging - Proceedings of SPIE
Volume8596
ISSN (Print)1605-7422

Other

OtherReporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications V
CountryUnited States
CitySan Francisco, CA
Period2/4/132/6/13

Keywords

  • Phosphatidylserine (PS)
  • breast cancer
  • glioma
  • near-infrared (NIR) optical imaging
  • tumor vasculature

ASJC Scopus subject areas

  • Electronic, Optical and Magnetic Materials
  • Biomaterials
  • Atomic and Molecular Physics, and Optics
  • Radiology Nuclear Medicine and imaging

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  • Cite this

    Zhao, D., Stafford, J. H., Zhou, H., & Thorpe, P. E. (2013). In vivo imaging of tumor vascular endothelial cells. In Reporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications V [859603] (Progress in Biomedical Optics and Imaging - Proceedings of SPIE; Vol. 8596). https://doi.org/10.1117/12.2007291