Hyperthermia and gene therapy: Potential use of MicroPET imaging
Hyperthermia and gene therapy: Potential use of MicroPET imaging
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DOI：
10.1080/02656730600784677
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发表时间：
2006-05-01
影响因子：
3.1
通讯作者：
Ling, CC
中科院分区：
文献类型：
--
作者：
Li, GC;He, FQ;Ling, CC
近年来，热疗和基因治疗都被认为是改善癌症放射治疗的方法。此外，还存在将这些方法结合起来以提高整体治疗效果的潜力。例如，据报道，腺病毒介导的热诱导基因表达可以降低与治疗基因的组成型控制表达相关的正常组织毒性。在我们的实验室中，我们已经证明腺病毒介导的热激活反义Ku70表达在体外和体内使肿瘤细胞放射增敏，这提出了一种使用热激活基因放射疗法使人类肿瘤放射增敏的新方法。然而，为了优化热激活基因放射疗法在临床中的应用，我们需要开发技术来改善治疗性腺病毒的递送并以非侵入方式验证/监测递送。在一项正在进行的研究中，我们测试了轻度热疗在改善小鼠肿瘤模型中腺病毒载体递送方面的效果。此外，我们评估了使用非侵入性 microPET 成像来监测腺病毒载体的传播。我们的初步结果表明，(1) microPET 成像可用于非侵入性监测病毒载体的传递和传播，(2) 轻度热休克可显着改善病毒载体的分布，换句话说，在体内实现更广泛的空间传播。在这里，我们将简要回顾热疗和热激活基因放射治疗的现状，以及 PET 成像在基因治疗中的潜在应用。
In recent years, both hyperthermia and gene-therapy have been evaluated as approaches to improve cancer radiotherapy. In addition, potential exists to combine these approaches to increase the overall therapeutic efficacy. For example, it has been reported that adenovirus-mediated heat-inducible gene expression may reduce the normal tissue toxicity associated with constitutively controlled expression of therapeutic genes. In our laboratory, we have shown that adenovirus-mediated, heat-activated antisense Ku70 expression radiosensitizes tumor cells in vitro and in vivo, suggesting a novel approach to use heat-activated gene-radiotherapy to radiosensitize human tumors.However, to optimize the application of heat-activated gene-radiotherapy in the clinic, we need to develop techniques to improve the delivery of the therapeutic adenovirus and to verify/monitor the delivery non-invasively. In an ongoing study we test the effect of mild hyperthermia in improving adenovirus-medicated vector delivery in a mouse tumor model. In addition, we evaluate the use of non-invasive microPET imaging to monitor the spread of the adenoviral vector. Our preliminary results show that (1) microPET imaging can be used to monitor non-invasively the viral vector delivery and dissemination, and (2) mild heat shock leads to significantly improved viral vector distribution, in other words, a wider spatial spread, in vivo.Here, we will present a short review on the current status of hyperthermia and heat-activated gene-radiotherapy, and the potential use of PET imaging in gene therapy.