Radiation-guided P-selectin antibody targeted to lung cancer.
OBJECTIVE
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.


METHODS
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.
Hariri
G
G
Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Zhang
Y
Y
Fu
A
A
Han
Z
Z
Brechbiel
M
M
Tantawy
M N
MN
Peterson
T E
TE
Mernaugh
R
R
Hallahan
D
D
D000818:Animals; D000912:Antibodies, Neoplasm / Q000378:metabolism*; D045744:Cell Line, Tumor; D004307:Dose-Response Relationship, Radiation; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism / Q000532:radiotherapy; D008297:Male; D051379:Mice; D008819:Mice, Nude; D019007:P-Selectin / Q000378:metabolism*; D011829:Radiation Dosage; D011877:Radionuclide Imaging; D011878:Radiotherapy / Q000379:methods*
D000912:Antibodies, Neoplasm; D019007:P-Selectin