We have developed a specific technique for imaging
cancer in vivo using Cy5.5-labeled
factor VIIa (fVIIa), clotting-deficient
FFRck-fVIIa,
paclitaxel-
FFRck-fVIIa, and anti-
tissue factor (TF) antibody. FVIIa is the natural
ligand for TF. We took advantage of the fact that vascular endothelial cells (VECs) in
cancer, but not normal tissue, aberrantly express TF due to its induction by
vascular endothelial growth factor (
VEGF). Under physiological conditions, TF is expressed by stromal cells and outer blood vessel layers (smooth muscle and adventitia), but not by VECs. We hypothesized that labeled fVIIa or anti-TF
antibodies could be used to image the
tumor vasculature in vivo. To test this, Cy5.5-labeled fVIIa,
FFRck-fVIIa,
paclitaxel-
FFRck-fVIIa, and anti-TF antibody were developed and administered to athymic nude mice carrying xenografts including
glioma U87EGFRviii,
pancreatic cancer ASPC-1 and Mia PaCa-2, and
squamous cell carcinoma KB-V1.
Cy5.5 labeled with these targeting
proteins specifically localized to the
tumor xenografts for at least 14 days but unconjugated
Cy5.5 did not localize to any xenografts or organs. This method of imaging TF in the
tumor VECs may be useful in detecting primary
tumors and
metastases as well as monitoring in vivo therapeutic responses.