Molecular Imaging Center, Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Department of Genetics, University of Groningen, Groningen, the Netherlands.
Med Res Rev. 2018 Sep;38(6):1713-1768. doi: 10.1002/med.21495. Epub 2018 Mar 12.
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.
成功治疗癌症患者需要平衡剂量、时间和治疗方案的类型。检测细胞死亡的增加可能是最终治疗成功的预测指标。因此，细胞死亡的成像可以导致早期识别治疗反应者和无反应者，并进行“个体化治疗”。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，尽管在目标选择、示踪剂药代动力学、目标与非目标比以及扫描的空间和时间分辨率方面仍存在未解决的问题。死亡细胞的磷脂酰丝氨酸暴露是研究最广泛的成像靶点。然而，用放射性标记的 Annexin A5 可视化此过程尚未成为临床常规。死亡模式的分类不再仅基于细胞形态学，还基于生物化学，并且细胞凋亡不再被认为是抗肿瘤治疗后细胞死亡的主要机制，如早期所认为的那样。这些概念上的变化影响了放射性化学研究。最近已经探索了针对膜通透性、细胞质 pH 值、线粒体膜电位或半胱氨酸天冬氨酸蛋白酶激活变化的新型探针。在这篇综述中，我们讨论了可以靶向以可视化细胞死亡的肿瘤中的分子变化，并提出了有前途的生物标志物供未来探索。
