Department of Nuclear Medicine, University Hospital Münster, Albert-Schweitzer-Str. 33, D-48149 Münster, Germany.
Anticancer Agents Med Chem. 2009 Nov;9(9):968-85. doi: 10.2174/187152009789377754.
The balance between proliferation and programmed cell death--apoptosis--is essential for multicellular organisms which use apoptosis to regulate and maintain the number and type of their cells during embryogenesis, growth and homeostasis. Increased cell proliferation or enhanced cell loss can be caused by dysregulated apoptosis and are observed in various diseases: in clinical scenarios such as neurodegenerative disorders, myocardial infarction and stroke the rate of apoptosis is upregulated compared to the physiological situation, while in clinical scenarios such as cancer or autoimmune diseases which are connected with pathological proliferation, apoptosis is often downregulated. Therefore, non-invasive imaging of apoptosis is of great clinical interest as patients would clearly benefit from the diagnosis of cell loss post infarction or from monitoring apoptosis triggered by chemotherapy or radiation therapy of tumours. Several biochemical transformations occur in apoptotic cells offering different biological targets for the development of specific molecular biomarkers of apoptosis. Key steps that occur during apoptosis have already been evaluated; among these are the externalisation of phospholipid phosphatidylserine to the outer leaflet of the cell membrane, which can be visualized by labeled annexin A5 and the activation of caspases, especially effector caspase-3, which can be addressed by labeled enzyme substrates or synthetic caspase inhibitors. Here, recent advances in tracer development for the molecular imaging techniques PET, SPECT and optical imaging are presented, the discussion of breakthroughs is involved, drawbacks and methodological issues of apoptosis imaging are highlighted.
细胞增殖与程序性细胞死亡（凋亡）之间的平衡对于多细胞生物至关重要，多细胞生物利用凋亡来调节和维持胚胎发生、生长和体内平衡过程中细胞的数量和类型。凋亡失调可导致细胞增殖增加或细胞丢失增强，并在各种疾病中观察到：在临床情况下，如神经退行性疾病、心肌梗死和中风，与生理情况相比，凋亡的速率上调，而在临床情况下，如与病理性增殖相关的癌症或自身免疫性疾病，凋亡通常下调。因此，凋亡的非侵入性成像具有重要的临床意义，因为患者将明显受益于梗死后细胞丢失的诊断，或受益于监测化疗或放射治疗肿瘤引发的凋亡。凋亡细胞中发生的几种生化转化为凋亡的特异性分子生物标志物的开发提供了不同的生物学靶标。已经评估了凋亡过程中发生的关键步骤；其中包括磷脂磷脂酰丝氨酸向细胞膜外叶的外化，这可以通过标记的膜联蛋白 A5可视化，以及半胱天冬酶的激活，特别是效应半胱天冬酶-3，可以通过标记的酶底物或合成的半胱天冬酶抑制剂来解决。本文介绍了用于正电子发射断层扫描（PET）、单光子发射计算机断层扫描（SPECT）和光学成像等分子成像技术的示踪剂开发的最新进展，讨论了突破点，并强调了凋亡成像的缺点和方法学问题。
