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Positron emission tomography imaging and biodistribution of vascular endothelial growth factor with 64Cu-labeled bevacizumab in colorectal cancer xenografts
- Source :
- Cancer science. 102(1)
- Publication Year :
- 2010
-
Abstract
- Vascular endothelial growth factor (VEGF) is considered to be a major angiogenic factor responsible for the development of tumor vasculature. The aim of this study was to image VEGF expression with (64)Cu-labeled anti-VEGF antibody (bevacizumab) non-invasively, and to see whether or not the expression was correlated with tumor accumulation in colorectal cancer xenografts. Bevacizumab was conjugated with the bifunctional chelator 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA) and radiolabeled with (64)Cu. In vivo biodistribution studies and positron emission tomography (PET) imaging were performed on mice bearing human colorectal cancer (HT29) xenografts after injection of (64)Cu-DOTA-bevacizumab, which showed clear accumulation of (64)Cu-DOTA-bevacizumab in the tumor (22.7 ± 1.0 %ID/g, 24 ± 0.2 %ID/g, 19.0 ± 2.5 %ID/g at 24, 48 and 72 h, respectively). Tumor accumulation of (64)Cu-DOTA-bevacizumab was significantly correlated with VEGF expression as measured by western blot (ρ = 0.81, P = 0.004). Vascular endothelial growth factor blocking with unlabeled bevacizumab significantly reduced tumor accumulation of (64) Cu-DOTA- bevacizumab (9.7 ± 1.2 %ID/g, P < 0.001) at 48 h. Interestingly, the blood concentration of VEGF in the mice treated with excess fold of bevacizumab was significantly higher than those without at 48 h (25.5 ± 4.6 %ID/g vs 6.5 ± 2.1 %ID/g, P = 0.0016). Liver uptake decreased from 24 h (17.2 ± 1.7 %ID/g) to 48 h (13.0 ± 4.2 %ID/g) and 72 h (10.6 ± 1.5 %ID/g) due to hepatic clearance of the tracer. The present study successfully showed (64) Cu-DOTA-bevacizumab as a potential PET tracer for non-invasive imaging of VEGF expression in colorectal cancer xenografts.
- Subjects :
- Vascular Endothelial Growth Factor A
Cancer Research
Biodistribution
Pathology
medicine.medical_specialty
Bevacizumab
Colorectal cancer
Blotting, Western
Transplantation, Heterologous
Antibodies, Monoclonal, Humanized
chemistry.chemical_compound
Mice
medicine
Animals
Humans
Tissue Distribution
Mice, Inbred BALB C
business.industry
Antibodies, Monoclonal
General Medicine
medicine.disease
Immunohistochemistry
Transplantation
Blot
Vascular endothelial growth factor
Vascular endothelial growth factor A
Oncology
chemistry
Copper Radioisotopes
Isotope Labeling
Positron-Emission Tomography
Cancer research
Female
Radiopharmaceuticals
business
HT29 Cells
Neoplasm Transplantation
medicine.drug
Subjects
Details
- ISSN :
- 13497006
- Volume :
- 102
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Cancer science
- Accession number :
- edsair.doi.dedup.....5f2e9983faf83715fca7fe70e6c3524a