de Vries E F J
Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands.
Curr Pharm Des. 2006;12(30):3847-56. doi: 10.2174/138161206778559650.
Cyclooxygenase is an enzyme that catalyzes the first two steps in the biosynthesis of prostanoids. The constitutively expressed isoform COX-1 is regarded as a housekeeping enzyme that is responsible for the normal production of prostanoids. The inducible isoform COX-2, on the other hand, is transiently induced during inflammation by various stimuli. Increasing evidence has shown that COX-2 is not only implicated in inflammation but also in oncogenesis. Overexpression of COX-2 has been observed in a variety of tumors. Prostaglandins produced by COX-2 affect important processes in carcinogenesis, including angiogenesis, tissue invasion, metastasis and apoptosis. Several studies indicate that COX-2 is also involved in neurological disorders, like Alzheimer's disease, Parkinson's disease and ischemia, where COX-2 overexpression leads to neurotoxicity. Many aspects of the role of COX-2 in (patho)physiology, however, remain unclear. At present, COX-2 expression is determined by ex vivo laboratory analysis, but the results could be greatly affected by the instability of COX-2 mRNA and protein and by sampling errors. A noninvasive imaging method to monitor COX-2 expression, like positron emission tomography (PET) or single photon emission computed tomography (SPECT), could overcome this complication and may provide novel insights in the role of COX-2, especially in neurological disorders where repetitive sampling is not possible. Such a technique could also be applied to the in vivo evaluation of novel selective COX-2 inhibitors and in dose-escalation studies. This review will present an overview of the developments in the recently emerging field of COX-2 imaging.
环氧化酶是一种催化前列腺素生物合成前两步的酶。组成型表达的同工型COX-1被视为一种管家酶，负责前列腺素的正常产生。另一方面，诱导型同工型COX-2在炎症期间会被各种刺激短暂诱导。越来越多的证据表明，COX-2不仅与炎症有关，还与肿瘤发生有关。在多种肿瘤中都观察到了COX-2的过表达。COX-2产生的前列腺素影响致癌过程中的重要环节，包括血管生成、组织侵袭、转移和细胞凋亡。多项研究表明，COX-2还参与神经疾病，如阿尔茨海默病、帕金森病和局部缺血，其中COX-2过表达会导致神经毒性。然而，COX-2在（病理）生理学中的作用的许多方面仍不清楚。目前，COX-2的表达是通过离体实验室分析来确定的，但结果可能会受到COX-2 mRNA和蛋白质的不稳定性以及采样误差的极大影响。一种监测COX-2表达的非侵入性成像方法，如正电子发射断层扫描（PET）或单光子发射计算机断层扫描（SPECT），可以克服这一复杂性，并可能为COX-2的作用提供新的见解，特别是在无法进行重复采样的神经疾病中。这种技术还可应用于新型选择性COX-2抑制剂的体内评估和剂量递增研究。本综述将概述COX-2成像这一新兴领域的发展情况。
