Comprehensive Cancer Imaging Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London, W12 0NN, UK.
Anticancer Agents Med Chem. 2009 Nov;9(9):958-67. doi: 10.2174/187152009789377709.
Deregulated apoptosis is involved in several diseases including myocardial infarction, ischemia and neurodegenerative disorders, which are characterized by excessive apoptosis. In contrast, resistance to apoptosis is defined as one of the hallmarks of cancer. It therefore follows that strategies that enable the quantitative detection of apoptosis modulation in vivo would be of enormous benefit in the clinic for diagnosis and patient management (evaluation of response to treatment). In addition, such strategies could be used to evaluate the efficacy of novel therapeutics along their development process. During the development of novel therapeutics it would be necessary to evaluate drug efficacy in vitro and then in experimental animal models and, ultimately, in clinical trials. Currently there is no one single probe that is suitable for imaging apoptosis at every stage of evaluation, necessitating a switch between probe types during the development process. This has key implications for the quality and reproducibility of the data obtained. The present review summarizes the development of new apoptosis detecting probes that have the potential for bridging different stages of the evaluation process such that accurate, translational apoptosis imaging data are obtained.
细胞凋亡失调与多种疾病相关,包括心肌梗死、缺血和神经退行性疾病,这些疾病的特征是细胞凋亡过度。相反,抗细胞凋亡被定义为癌症的标志之一。因此,能够在体内定量检测细胞凋亡调节的策略将对临床诊断和患者管理(评估治疗反应)有巨大的益处。此外,这些策略可用于在开发过程中评估新型治疗药物的疗效。在新型治疗药物的开发过程中,有必要在体外评估药物疗效,然后在实验动物模型中进行评估,最终在临床试验中进行评估。目前,没有一种单一的探针适用于在评估的每个阶段成像细胞凋亡,因此在开发过程中需要在探针类型之间进行切换。这对获得的数据的质量和可重复性有重要影响。本综述总结了新的细胞凋亡检测探针的开发,这些探针有可能在评估过程的不同阶段之间架起桥梁,从而获得准确的、可转化的细胞凋亡成像数据。