Development of radiocontrast agents for vascular imaging: Progress to date

被引:4
作者
Blankenberg F.G. [1 ]
Mari C. [1 ]
Strauss H.W. [2 ]
机构
[1] Department of Radiology, Division of Pediatric Radiology, L. Salter Packard Children's Hosp., Stanford, CA
[2] Department of Radiology, Division of Nuclear Medicine, Memorial Sloan Kettering Cancer Ctr., New York, NY
基金
美国国家卫生研究院;
关键词
Vulnerable Plaque; Atheromatous Lesion; Cardiac Allograft Rejection; Label Annexin Versus; Depreotide;
D O I
10.2165/00129784-200202060-00001
中图分类号
学科分类号
摘要
The revolution in molecular imaging techniques is profoundly changing the understanding of the pathophysiology and treatment of atherosclerosis. With these rapid changes there is an increasing demand for development of sensitive and well tolerated novel imaging agents that can be rapidly translated from small animal models into patients with atherosclerosis. Nuclear medicine and positron emission tomography techniques have the ability to detect and serially monitor a variety of biologic and pathophysiologic processes usually with tracer quantities of radiolabeled peptides, drugs, and other molecules at dosages free of pharmacologic adverse effects unlike the current generation of intravenous agents required for magnetic resonance imaging (MRI) and computed axial tomography (CT) scanning. A representative sampling of the wide array of radiopharmaceuticals developed specifically for radionuclide imaging of atherosclerosis, that have been approved for clinical use and those in pre-clinical trials, have been reviewed in this article. The presence of an inflammatory stimulus increases expression of CC (cysteine-cysteine motif) chemokine receptor (CCR)-2 on monocytes and macrophages, and somatostatin receptors on T lymphocytes. Radiolabeled monocyte chemoattractant protein (MCP)-1 binds with high affinity to CCR-2 and can be used to detect subacute and chronic inflammatory lesions. Similarly, radiolabeled octreotide or depreotide can be used to detect activated T lymphocytes which may identify the vulnerable plaque. Animal models indicate that 99mTc-annexin V, 125I-MCP-1 and [18F]-fluoro-2-deoxyglucose are effective in identifying apoptotic cell death, macrophage infiltration and metabolic activity in atheromatous lesions, respectively. Expression of αvβ3 integrin is increased in activated endothelial cells and vascular smooth muscle cells after vascular injury, and αvβ3 integrin is minimally expressed on smooth muscle cells and is not expressed on quiescent epithelial cells. Radiolabeled high-affinity peptides can be used to target the αvβ3 integrin and visualize areas of vascular damage. Advances in technology such as the micro-single photon emission computed tomography (microSPECT) have the potential to overcome the drawbacks of older CT and MRImethodologies, such as lack of biologically relevant ligands and compatible blood pool contrast agents for imaging. Despite these advances in imaging technology, the small size of atheromatous lesions makes it difficult to detect using external imaging techniques. Therefore, recently there has been renewed interest in the use of intravascular catheter-based radiation detectors.
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页码:357 / 365
页数:8
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