Characterizing vascular parameters in hypoxic regions: a combined magnetic resonance and optical imaging study of a human prostate cancer model.
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.
Raman
Venu
V
The Johns Hopkins University, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Artemov
Dmitri
D
Pathak
Arvind P
AP
Winnard
Paul T
PT
McNutt
Stephen
S
Yudina
Anna
A
Bogdanov
Alexei
A
Bhujwalla
Zaver M
ZM
D000818:Animals; D015687:Cell Hypoxia / Q000235:genetics / Q000502:physiology; D045744:Cell Line, Tumor; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D018810:Magnetic Resonance Angiography / Q000379:methods*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D010100:Oxygen / Q000378:metabolism; D037121:Plant Lectins / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics; D011471:Prostatic Neoplasms / Q000098:blood supply* / Q000235:genetics / Q000378:metabolism; D020218:Response Elements; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism
D037121:Plant Lectins; D042461:Vascular Endothelial Growth Factor A; C034981:tomato lectin; D049452:Green Fluorescent Proteins; D010100:Oxygen