Radiation-guided P-selectin antibody targeted to lung cancer

G. Hariri, Y. Zhang, A. Fu, Z. Han, M. Brechbiel, M. N. Tantawy, T. E. Peterson, R. Mernaugh, D. Hallahan

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Purpose: P-selectin expression is significantly increased in tumor microvasculature following exposure to ionizing radiation. The purpose of this study was to image radiation-induced P-selectin expression in vivo using optical imaging and gamma camera imaging in a heterotopic lung cancer model by using ScFv antibodies to P-selectin. Procedures: In vitro studies using endothelial cells were done using 3 Gy radiation and selected ScFv antibodies to P-selectin. In vivo studies were performed using Lewis lung carcinoma cells subcutaneously injected into the hind limbs of nude mice. Mice were treated with 6 Gy radiation and sham radiation 10 days post-inoculation. P-selectin expression was assessed with near-infrared imaging using Cy7 labeled antibody, and gamma camera imaging using 111In-DTPA labeled antibody. Results: In vitro studies showed antibody binding to P-selectin in radiation treated endothelial cells. In vivo optical imaging and gamma camera imaging studies showed significant tumor-specific binding to P-selectin in irradiated tumors compared to unirradiated tumors. Conclusions: Optical imaging and gamma camera imaging are effective methods for visualizing in vivo targeting of radiation-induced P-selectin in lung tumors. This study suggests that fluorescent-labeled and radiolabeled ScFv antibodies can be used to target radiation-induced P-selectin for the tumor-specific delivery of therapeutic drugs and radionuclides in vivo.

Original languageEnglish
Pages (from-to)821-830
Number of pages10
JournalAnnals of biomedical engineering
Volume36
Issue number5
DOIs
StatePublished - May 2008

Keywords

  • Lung cancer
  • Nuclear imaging
  • Optical imaging
  • P-selectin
  • Radiation

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