Targeted in vivo labeling of receptors for vascular endothelial growth factor: approach to identification of ischemic tissue

A method for identifying tissue experiencing hypoxic stress due to atherosclerotic vascular disease would be clinically useful. Vascular endothelial growth factor-121 (VEGF121) is an angiogenic protein secreted in response to hypoxia that binds to VEGF receptors overexpressed by ischemic microvascul...

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Bibliographic Details
Published in:Circulation (New York, N.Y.) N.Y.), 2003-07, Vol.108 (1), p.97-103
Main Authors: Lu, Erxiong, Wagner, William R, Schellenberger, Ute, Abraham, Judith A, Klibanov, Alexander L, Woulfe, Steven R, Csikari, Melissa M, Fischer, David, Schreiner, George F, Brandenburger, Gary H, Villanueva, Flordeliza S
Format: Article
Language:English
Subjects:
Animals
Binding, Competitive
Disease Models, Animal
Endothelial Growth Factors - pharmacokinetics
Femoral Artery - physiopathology
Hindlimb - blood supply
Hindlimb - diagnostic imaging
Immunohistochemistry
Indium Radioisotopes
Intercellular Signaling Peptides and Proteins - pharmacokinetics
Ischemia - diagnostic imaging
Ischemia - pathology
Ischemia - physiopathology
Lymphokines - pharmacokinetics
Metabolic Clearance Rate
Muscle, Skeletal - blood supply
Muscle, Skeletal - diagnostic imaging
Muscle, Skeletal - physiopathology
Predictive Value of Tests
Rabbits
Radionuclide Imaging
Receptors, Vascular Endothelial Growth Factor - metabolism
Scintillation Counting
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors
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Summary:A method for identifying tissue experiencing hypoxic stress due to atherosclerotic vascular disease would be clinically useful. Vascular endothelial growth factor-121 (VEGF121) is an angiogenic protein secreted in response to hypoxia that binds to VEGF receptors overexpressed by ischemic microvasculature. We tested the hypothesis that VEGF receptors could serve as markers for ischemic tissue and hence provide a target for imaging such tissue with radiolabeled human VEGF121. A rabbit model of unilateral hindlimb ischemia was created by femoral artery excision (n=14). Control rabbits (n=5) underwent identical surgery without femoral excision. On postoperative day 10, rabbits were intravenously administered 100 microCi of 111In-labeled recombinant human VEGF121, and biodistribution studies and planar imaging were conducted at 3, 24, and 48 hours. On postmortem gamma counting, there was greater accumulation of 111In-labeled VEGF121 in ischemic than in control tissue (P
ISSN:0009-7322
1524-4539
DOI:10.1161/01.CIR.0000079100.38176.83