Targeted in vivo labeling of receptors for vascular endothelial growth factor - Approach to identification of ischemic tissue

Article

关键词: TC-99M-LABELED NITROIMIDAZOLE BMS-181321;    ATHEROSCLEROTIC LESIONS;    NONINVASIVE DETECTION;    MONOCLONAL-ANTIBODY;    VEGF RECEPTORS;    HYPOXIA;    ANGIOGENESIS;    EXPRESSION;    CELLS;    MODULATION;   

DOI  :  10.1161/01.CIR.0000079100.38176.83

来源: SCIE

【 摘 要 】

Background-A method for identifying tissue experiencing hypoxic stress due to atherosclerotic vascular disease would be clinically useful. Vascular endothelial growth factor-121 (VEGF(121)) 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 VEGF(121). Methods and Results-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 muCi of In-111-labeled recombinant human VEGF(121), and biodistribution studies and planar imaging were conducted at 3, 24, and 48 hours. On postmortem gamma counting, there was greater accumulation of In-111-labeled VEGF(121) in ischemic than in control tissue (P<0.02). Differential uptake of isotope by ischemic muscle was not seen in rabbits injected with I-125-labeled human serum albumin (n=6). Radioactivity imaged in hindlimb regions of interest was significantly higher in ischemic muscle than in sham-operated and contralateral nonoperated hindlimb at 3 hours (P<0.02). Immunohistochemical staining confirmed upregulation of VEGF receptors in ischemic skeletal muscle. Conclusions-Identification of the ischemic state via targeted radiolabeling of hypoxia-induced angiogenic receptors is possible. This approach could be useful for monitoring the efficacy of revascularization strategies such as therapeutic angiogenesis.

【 授权许可】

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