Department of Chemistry and Biochemistry, Notre Dame Integrated Imaging Facility, 236 Nieuwland Science Hall, University of Notre Dame, Notre Dame, IN 46556, USA.
Bioconjug Chem. 2012 Oct 17;23(10):1989-2006. doi: 10.1021/bc3003309. Epub 2012 Sep 26.
Cell death is a critically important biological process. Disruption of homeostasis, either by excessive or deficient cell death, is a hallmark of many pathological conditions. Recent research advances have greatly increased our molecular understanding of cell death and its role in a range of diseases and therapeutic treatments. Central to these ongoing research and clinical efforts is the need for imaging technologies that can locate and identify cell death in a wide array of in vitro and in vivo biomedical samples with varied spatiotemporal requirements. This review article summarizes community efforts over the past five years to identify useful biomarkers for dead and dying cells, and to develop molecular probes that target these biomarkers for optical, radionuclear, or magnetic resonance imaging. Apoptosis biomarkers are classified as either intracellular (caspase enzymes, mitochondrial membrane potential, cytosolic proteins) or extracellular (plasma membrane phospholipids, membrane potential, surface exposed histones). Necrosis, autophagy, and senescence biomarkers are described, as well as unexplored cell death biomarkers. The article discusses possible chemotherapeutic and theranostic strategies, and concludes with a summary of current challenges and expected eventual rewards of clinical cell death imaging.
细胞死亡是一个至关重要的生物学过程。无论是细胞死亡过多还是过少导致的内环境稳态破坏,都是许多病理状况的标志。最近的研究进展极大地提高了我们对细胞死亡及其在一系列疾病和治疗中的作用的分子理解。这些正在进行的研究和临床努力的核心是需要成像技术,以便在具有不同时空要求的各种体外和体内生物医学样本中定位和识别细胞死亡。本文综述了过去五年中社区在识别死亡和濒死细胞的有用生物标志物以及开发针对这些生物标志物的分子探针方面的努力,这些探针可用于光学、放射性核素或磁共振成像。凋亡生物标志物分为细胞内(半胱天冬酶酶、线粒体膜电位、细胞质蛋白)或细胞外(质膜磷脂、膜电位、表面暴露组蛋白)。本文还描述了坏死、自噬和衰老生物标志物,以及未探索的细胞死亡生物标志物。文章讨论了可能的化疗和治疗策略,并总结了临床细胞死亡成像的当前挑战和预期最终回报。