Blankenberg Francis G, Mari Carina, Strauss H William
Department of Radiology/Division of Pediatric Radiology, Lucile Salter Packard Children's Hospital, Stanford, California, USA.
Am J Cardiovasc Drugs. 2002;2(6):357-65. doi: 10.2165/00129784-200202060-00001.
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 (99m)Tc-annexin V, (125)I-MCP-1 and [(18)F]-fluoro-2-deoxyglucose are effective in identifying apoptotic cell death, macrophage infiltration and metabolic activity in atheromatous lesions, respectively. Expression of alpha(v)beta(3) integrin is increased in activated endothelial cells and vascular smooth muscle cells after vascular injury, and alpha(v)beta(3) 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 alpha(v)beta(3) 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 MRI methodologies, 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.
分子成像技术的革命正在深刻改变人们对动脉粥样硬化病理生理学和治疗方法的理解。随着这些快速变化，对开发敏感且耐受性良好的新型成像剂的需求日益增加，这些成像剂能够从小动物模型快速转化应用于动脉粥样硬化患者。核医学和正电子发射断层扫描技术有能力检测并连续监测各种生物和病理生理过程，通常使用示踪量的放射性标记肽、药物和其他分子，其剂量不会产生药理学不良反应，这与磁共振成像（MRI）和计算机断层扫描（CT）扫描所需的新一代静脉注射剂不同。本文对专门为动脉粥样硬化放射性核素成像开发的、已获临床批准以及处于临床前试验阶段的各类放射性药物进行了代表性抽样综述。炎症刺激的存在会增加单核细胞和巨噬细胞上CC（半胱氨酸 - 半胱氨酸基序）趋化因子受体（CCR）-2以及T淋巴细胞上生长抑素受体的表达。放射性标记的单核细胞趋化蛋白（MCP）-1与CCR-2具有高亲和力结合，可用于检测亚急性和慢性炎症病变。同样，放射性标记的奥曲肽或地普奥肽可用于检测活化的T淋巴细胞，这可能有助于识别易损斑块。动物模型表明，（99m）Tc - 膜联蛋白V、（125）I - MCP -1和[（18）F] - 氟 - 2 - 脱氧葡萄糖分别在识别动脉粥样硬化病变中的凋亡细胞死亡、巨噬细胞浸润和代谢活性方面有效。α（v）β（3）整合素在血管损伤后活化的内皮细胞和平滑肌细胞中表达增加，而在平滑肌细胞上α（v）β（3）整合素表达极少，在静止的上皮细胞上则不表达。放射性标记的高亲和力肽可用于靶向α（v）β（3）整合素并可视化血管损伤区域。诸如微单光子发射计算机断层扫描（microSPECT）等技术进步有可能克服旧的CT和MRI方法的缺点，例如缺乏用于成像的生物学相关配体和兼容的血池造影剂。尽管成像技术有这些进步，但动脉粥样硬化病变的尺寸较小，难以使用外部成像技术检测。因此，最近人们对使用基于血管内导管的辐射探测器重新产生了兴趣。
