Radiation-Guided P-Selectin Antibody Targeted to Lung Cancer

• Published in: Annals of biomedical engineering 2008-05, Vol.36 (5), p.821-830
• Main Authors: Hariri, G., Zhang, Y., Fu, A., Han, Z., Brechbiel, M., Tantawy, M. N., Peterson, T. E., Mernaugh, R., Hallahan, D.
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Neoplasm - metabolism; Biochemistry; Biological and Medical Physics; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Biophysics; Cameras; Cell Line, Tumor; Classical Mechanics; Dose-Response Relationship, Radiation; Infrared imaging; Ionizing radiation; Lung cancer; Lung Neoplasms - diagnostic imaging; Lung Neoplasms - metabolism; Lung Neoplasms - radiotherapy; Male; Mice; Mice, Nude; P-Selectin - metabolism; Radiation Dosage; Radionuclide Imaging; Radiotherapy - methods; Tumors
• ISSN: 0090-6964; 1573-9686; 1521-6047
• DOI: 10.1007/s10439-008-9444-9

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 111 In-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 .