Detection of vascular endothelial growth factor in colon cancer xenografts using bevacizumab based near infrared fluorophore conjugate.
BACKGROUND
The aim of this study was to develop the near infrared fluorescence (NIRF)-based imaging agent for the visualization of vascular endothelial growth factor (VEGF) in colon cancer. AlexaFluor 750 conjugating with bevacizumab, and injected intravenously into nude mice bearing VEGF over-expressing HT29 human colorectal cancer. Optical imaging was performed at 15 min, 24 h and 48 h post injection. Immunofluorescences staining of the tumor sections were performed. HT29 colorectal cancer xenografts were clearly visualized with bevacizumab-AlexaFluor 750.


RESULTS
Ex vivo analysis showed 2.1 ± 0.4%, 37.6 ± 6.3% and 38.5 ± 6.2% injected dose/g accumulated in the tumors at 15 min, 24 h and 48 h respectively. Tumor uptake was significantly decreased in pretreated with excess of bevacizumab (p = 0.002). Immunofluorescence analysis showed strong staining of anti-CD 31 antibody around the blood vessels. Anti-VEGF-A and bevacizumab showed heterogeneous expression throughout the tumor.


CONCLUSIONS
Current study successfully detected the VEGF expression in HT29 colorectal cancer xenografts, signifying as a potential agent for non-invasive imaging of VEGF expression, which may be applied in clinical practice.
Department of Radiology, Thomas Jefferson University, Philadelphia, PA 19107, USA. bishnuhari.paudyal@jefferson.edu.
Bishnuhari
B
Paudyal
Pramila
P
Paudyal
Dilip
D
Shah
Hideyuki
H
Tominaga
Yoshito
Y
Tsushima
Keigo
K
Endo
D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000737:chemistry; D000068258:Bevacizumab; D003110:Colonic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D003952:Diagnostic Imaging; D005456:Fluorescent Dyes / Q000737:chemistry; D015972:Gene Expression Regulation, Neoplastic; D019073:HT29 Cells; D006801:Humans; D051379:Mice; D019265:Spectroscopy, Near-Infrared; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000302:isolation & purification*; D023041:Xenograft Model Antitumor Assays
D061067:Antibodies, Monoclonal, Humanized; D005456:Fluorescent Dyes; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab