Tumor vascular permeability to a nanoprobe correlates to tumor-specific expression levels of angiogenic markers

Files
bme_bella_002.pdf (2.42 MB)
Author(s)
Karathanasis, Efstathios
Chan, Leslie
Karumbaiah, Lohitash
McNeeley, Kathleen
D’Orsi, Carl J.
Annapragada, Ananth V.
Sechopoulos, Ioannis S.
Advisor(s)
Editor(s)
Associated Organization(s)
Organizational Unit
Wallace H. Coulter Department of Biomedical Engineering
The joint Georgia Tech and Emory department was established in 1997
Organizational Unit
Series
Collections
Research Publications
Supplementary to:
Permanent Link
http://hdl.handle.net/1853/47466
Abstract
Background. Vascular endothelial growth factor (VEGF) receptor-2 is the major mediator of the mitogenic, angiogenic, and vascular hyperpermeability effects of VEGF on breast tumors. Overexpression of VEGF and VEGF receptor-2 is associated with the degree of pathomorphosis of the tumor tissue and unfavorable prognosis. In this study, we demonstrate that non-invasive quantification of the degree of tumor vascular permeability to a nanoprobe correlates with the VEGF and its receptor levels and tumor growth. Methodology/Principal Findings. We designed an imaging nanoprobe and a methodology to detect the intratumoral deposition of a 100 nm-scale nanoprobe using mammography allowing measurement of the tumor vascular permeability in a rat MAT B III breast tumor model. The tumor vascular permeability varied widely among the animals. Notably, the VEGF and VEGF receptor-2 gene expression of the tumors as measured by qRT-PCR displayed a strong correlation to the imaging-based measurements of vascular permeability to the 100 nm-scale nanoprobe. This is in good agreement with the fact that tumors with high angiogenic activity are expected to have more permeable blood vessels resulting in high intratumoral deposition of a nanoscale agent. In addition, we show that higher intratumoral deposition of the nanoprobe as imaged with mammography correlated to a faster tumor growth rate. This data suggest that vascular permeability scales to the tumor growth and that tumor vascular permeability can be a measure of underlying VEGF and VEGF receptor-2 expression in individual tumors. Conclusions/Significance. This is the first demonstration, to our knowledge, that quantitative imaging of tumor vascular permeability to a nanoprobe represents a form of a surrogate, functional biomarker of underlying molecular markers of angiogenesis
Sponsor
Date
2009
Extent
Resource Type
Text
Resource Subtype
Article
Rights Statement
Rights URI