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Avenues to molecular imaging of dying cells: Focus on cancer
Medicinal Research Reviews ( IF 10.9 ) Pub Date : 2018-03-12 , DOI: 10.1002/med.21495
Anna A. Rybczynska 1, 2 , Hendrikus H. Boersma 1, 3 , Steven de Jong 4 , Jourik A. Gietema 4 , Walter Noordzij 1 , Rudi A. J. O. Dierckx 1, 5 , Philip H. Elsinga 1 , Aren van Waarde 1
Affiliation  

Successful treatment of cancer patients requires balancing of the dose, timing, and type of therapeutic regimen. Detection of increased cell death may serve as a predictor of the eventual therapeutic success. Imaging of cell death may thus lead to early identification of treatment responders and nonresponders, and to “patient‐tailored therapy.” Cell death in organs and tissues of the human body can be visualized, using positron emission tomography or single‐photon emission computed tomography, although unsolved problems remain concerning target selection, tracer pharmacokinetics, target‐to‐nontarget ratio, and spatial and temporal resolution of the scans. Phosphatidylserine exposure by dying cells has been the most extensively studied imaging target. However, visualization of this process with radiolabeled Annexin A5 has not become routine in the clinical setting. Classification of death modes is no longer based only on cell morphology but also on biochemistry, and apoptosis is no longer found to be the preponderant mechanism of cell death after antitumor therapy, as was earlier believed. These conceptual changes have affected radiochemical efforts. Novel probes targeting changes in membrane permeability, cytoplasmic pH, mitochondrial membrane potential, or caspase activation have recently been explored. In this review, we discuss molecular changes in tumors which can be targeted to visualize cell death and we propose promising biomarkers for future exploration.

中文翻译:

垂死细胞分子成像的途径:关注癌症

癌症患者的成功治疗需要平衡剂量,时间和治疗方案的类型。细胞死亡增加的检测可以作为最终治疗成功的预测指标。细胞死亡的影像学检查可能因此导致及早发现治疗反应者和非反应者,并导致“针对患者的治疗”。可以使用正电子发射断层扫描或单光子发射计算机断层扫描来可视化人体器官和组织中的细胞死亡,但仍存在尚未解决的问题,包括靶标选择,示踪剂药代动力学,靶标与非靶标比以及靶标的时空分辨率扫描。垂死细胞对磷脂酰丝氨酸的暴露一直是研究最广泛的成像靶标。然而,在临床环境中,用放射性标记的膜联蛋白A5可视化该过程尚未成为常规操作。死亡模式的分类不再仅仅基于细胞形态,还基于生物化学,并且如先前所认为的,凋亡也不再被认为是抗肿瘤治疗后细胞死亡的主要机制。这些概念上的改变影响了放射化学的努力。最近研究了针对膜通透性,细胞质pH,线粒体膜电位或半胱天冬酶激活变化的新型探针。在这篇综述中,我们讨论了肿瘤中的分子变化,可将其可视化以观察细胞死亡,并提出了有希望的生物标记物,以供将来探索。就像早先所相信的,凋亡已不再是抗肿瘤治疗后细胞死亡的主要机制。这些概念上的改变影响了放射化学的努力。最近研究了针对膜通透性,细胞质pH,线粒体膜电位或半胱天冬酶激活变化的新型探针。在这篇综述中,我们讨论了肿瘤中的分子变化,可将其可视化以观察细胞死亡,并提出了有希望的生物标记物,以供将来探索。正如早先所相信的,凋亡已不再是抗肿瘤治疗后细胞死亡的主要机制。这些概念上的改变影响了放射化学的努力。最近研究了针对膜通透性,细胞质pH,线粒体膜电位或半胱天冬酶激活变化的新型探针。在这篇综述中,我们讨论了肿瘤中的分子变化,可将其可视化以观察细胞死亡,并提出了有希望的生物标记物,以供将来探索。
更新日期:2018-03-12
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