Non-invasive PET and SPECT imaging of tissue hypoxia using isotopically labeled 2-nitroimidazoles.
Non-invasive PET and SPECT imaging of tissue hypoxia using isotopically labeled 2-nitroimidazoles.
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DOI：
10.1007/978-1-4615-0205-0_47
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发表时间：
2003
影响因子：
--
通讯作者：
C. Koch;S. Evans
中科院分区：
文献类型：
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作者：
C. Koch;S. Evans
病理学低水平组织pO 2的测量是确定许多临床重要疾病（包括心血管功能不全、中风和癌症）预后的重要诊断目标。以2-硝基咪唑为代表的一类生物还原活化药物具有很好的应用潜力。这类药物以在严重缺氧（例如低于0.05%氧）条件下最大的速率与细胞结合，并根据Michaelis-Menten动力学随氧浓度增加而被抑制。药物加合物存在许多检测可能性，包括可以以细胞到细胞分辨率测量组织切片中的药物加合物的侵入性测定。在非侵入性测定中使用这样的试剂是重要的，并且为此，许多药物已经与适合于通过核医学技术检测的放射性同位素缀合。与侵入性测定相比，非侵入性测定的分辨率和对比度更有限。因此，有许多因素有助于平衡2-硝基咪唑药物作为缺氧检测器的非侵入性与侵入性使用的利弊。这些因素将在本次审查中进行总结，重点是适合临床使用的化合物。将描述使用F标记的EF 5（使用侵入性测定的当前临床试验中的药物）的PET（正电子发射断层扫描）成像。
The measurement of pathologically low levels of tissue pO2 is an important diagnostic goal for determining the prognosis of many clinically important diseases including cardiovascular insufficiency, stroke and cancer. A class of bioreductively activated drugs, typified by the 2-nitroimidazoles, has excellent potential for application to this goal. Such drugs bind to cells at a rate which is maximal under conditions of severe hypoxia (e.g. less than 0.05% oxygen) and is inhibited, with Michaelis-Menten kinetics, as a function of increasing oxygen concentration. A number of detection possibilities exist for the drug adducts, including invasive assays which can measure drug adducts in tissue sections at cell-to-cell resolution. Use of such agents in noninvasive assays is important and, to this end, a number of drugs have been conjugated with radioactive isotopes suitable for detection by Nuclear Medicine techniques. In contrast with the invasive assays, resolution and contrast is much more limited with the non-invasive assays. Thus, there are many factors contributing to the balance of pros and cons for the non-invasive vs. invasive use of 2-nitroimidazole drugs as hypoxia detectors. These factors will be summarized in this review, with emphasis on compounds suitable for clinical use. PET (positron emission tomography) imaging with F-labeled EF5 (a drug in current clinical trials using invasive assays) will be described.