Richard Dimbleby Department of Cancer Research, Randall Division & Division of Cancer Studies, King's College London, Guy's Medical School Campus, London, SE1 1UL, UK.
Integr Biol (Camb). 2011 Jun;3(6):603-31. doi: 10.1039/c0ib00131g. Epub 2011 May 4.
We review novel, in vivo and tissue-based imaging technologies that monitor and optimize cancer therapeutics. Recent advances in cancer treatment centre around the development of targeted therapies and personalisation of treatment regimes to individual tumour characteristics. However, clinical outcomes have not improved as expected. Further development of the use of molecular imaging to predict or assess treatment response must address spatial heterogeneity of cancer within the body. A combination of different imaging modalities should be used to relate the effect of the drug to dosing regimen or effective drug concentration at the local site of action. Molecular imaging provides a functional and dynamic read-out of cancer therapeutics, from nanometre to whole body scale. At the whole body scale, an increase in the sensitivity and specificity of the imaging probe is required to localise (micro)metastatic foci and/or residual disease that are currently below the limit of detection. The use of image-guided endoscopic biopsy can produce tumour cells or tissues for nanoscopic analysis in a relatively patient-compliant manner, thereby linking clinical imaging to a more precise assessment of molecular mechanisms. This multimodality imaging approach (in combination with genetics/genomic information) could be used to bridge the gap between our knowledge of mechanisms underlying the processes of metastasis, tumour dormancy and routine clinical practice. Treatment regimes could therefore be individually tailored both at diagnosis and throughout treatment, through monitoring of drug pharmacodynamics providing an early read-out of response or resistance.
我们回顾了新型的、基于活体和组织的成像技术,这些技术可以监测和优化癌症治疗方法。癌症治疗的最新进展集中在靶向治疗的发展和针对个体肿瘤特征的治疗方案的个性化上。然而,临床结果并没有如预期的那样得到改善。进一步开发利用分子成像来预测或评估治疗反应,必须解决体内癌症的空间异质性问题。应结合不同的成像方式,将药物的作用与给药方案或在作用部位的有效药物浓度联系起来。分子成像提供了对癌症治疗的功能和动态评估,从纳米到全身尺度。在全身尺度上,需要提高成像探针的灵敏度和特异性,以定位(微)转移性病灶和/或目前低于检测限的残留疾病。图像引导的内镜活检的使用可以以相对患者依从的方式产生肿瘤细胞或组织,用于纳米级分析,从而将临床成像与对分子机制的更精确评估联系起来。这种多模态成像方法(结合遗传学/基因组信息)可用于弥合我们对转移、肿瘤休眠和常规临床实践过程中机制的认识之间的差距。因此,可以通过监测药物药效动力学,在诊断时和整个治疗过程中为每个患者量身定制治疗方案,从而提供对反应或耐药性的早期评估。