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Characterizing Vascular Parameters in Hypoxic Regions: A Combined Magnetic Resonance and Optical Imaging Study of a Human Prostate Cancer Model

¹ The Johns Hopkins University In vivo Cellular Molecular Imaging Center Program, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland and ² Department of Radiology, University of Massachusetts Medical School, Worcester, Massachusetts

Requests for reprints: Zaver M. Bhujwalla, Department of Radiology, The Johns Hopkins University School of Medicine, Room 208C Traylor Building, 720 Rutland Avenue, Baltimore, MD 21205. Phone: 410-955-9698; Fax: 410-614-1948; E-mail: zaver{at}mri.jhu.edu.

The integration of imaging technologies with the capabilities of genetic engineering has created novel opportunities for understanding and imaging cancer. Here, we have combined vascular magnetic resonance imaging (MRI) and optical imaging to understand the relationship between hypoxia and vascularization in a human prostate cancer model engineered to express enhanced green fluorescent protein (EGFP) under hypoxia. Characterization and validation of EGFP expression under hypoxic conditions was done in culture and in solid tumors in vivo. MRI measurements showed that vascular volume was significantly lower in fluorescing regions. These regions also frequently exhibited high permeability. These data were further supported by the detection of low vessel density in EGFP-positive regions, as determined by the distribution of intravascularly administered, fluorescence-labeled Lycopersicon esculentum lectin in frozen tumor sections. These observations are consistent with the possibility that regions of low vascular volumes are hypoxic, which induces increased expression of functionally active vascular endothelial growth factor, a potent vascular permeability factor. (Cancer Res 2006; 12(20): 9929-36)

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