文章：

临床前癌症成像的发展：创新疗法的发现

Developments in preclinical cancer imaging: innovating the discovery of therapeutics

原文发布日期：2014-04-17

DOI: 10.1038/nrc3724

类型: Review Article

开放获取: 否

要点：

1. Advanced fluorescence-based imaging, three-dimensional intermediate systems and intravital mouse models can be integrated into the standard drug project operating model (DPOM) to better inform the development and selection of new candidate drugs.
2. Intermediate systems provide initial three-dimensional imaging early in the drug discovery process to support translational cancer research in more physiologically relevant in vitro settings and identify deficient or ineffective drug strategies earlier in the drug discovery pipeline.
3. In vivo advanced imaging techniques can be used to assess more complex questions, such as transient protein–protein interactions or molecular, cell or tissue-specific dynamics in response to drug treatment in live tissue.
4. Biosensors are now providing dynamic and reversible fluorescence-based readouts of drug targeting, allowing drug turnover, clearance and dissociation to be monitored in real-time.
5. Stromal targeting of the tumour microenvironment is a vital aspect of cancer drug development, which can be quantified using advanced imaging techniques, such as second harmonic generation (SHG), third harmonic generation (THG) and fluorescence lifetime imaging microscopy (FLIM).
6. Longitudinal imaging through intravital imaging windows can give quantitative functional information from repeated, non-invasive imaging and drug endpoint analysis in real-time.

要点翻译：

1. 基于荧光的先进成像技术、三维中间系统和活体小鼠模型可整合至标准药物项目操作模式中，以更好地指导新候选药物的开发与筛选。
2. 中间系统能在药物发现早期提供三维成像支持，在更具生理相关性的体外环境中推进转化癌症研究，并在药物研发流程更早阶段识别缺陷性或无效的药物治疗策略。
3. 活体先进成像技术可用于评估更复杂的问题，例如活体组织中瞬时蛋白质相互作用，或分子、细胞及组织特异性动态对药物治疗的响应。
4. 生物传感器目前可提供药物靶向的动态可逆荧光读数，实现对药物代谢、清除与解离过程的实时监测。
5. 肿瘤微环境的基质靶向是癌症药物研发的关键环节，可通过二次谐波产生、三次谐波产生及荧光寿命成像显微镜等先进成像技术进行量化分析。
6. 通过活体成像窗口进行纵向成像，能够从重复性无创成像和实时药物终点分析中获取定量功能信息。

英文摘要：

Integrating biological imaging into early stages of the drug discovery process can provide invaluable readouts of drug activity within complex disease settings, such as cancer. Iterating this approach from initial lead compound identification in vitro to proof-of-principle in vivo analysis represents a key challenge in the drug discovery field. By embracing more complex and informative models in drug discovery, imaging can improve the fidelity and statistical robustness of preclinical cancer studies. In this Review, we highlight how combining advanced imaging with three-dimensional systems and intravital mouse models can provide more informative and disease-relevant platforms for cancer drug discovery.

摘要翻译： 

将生物影像整合到药物发现的早期阶段，可在癌症等复杂疾病环境中为药物活性提供宝贵读数。从体外先导化合物筛选到体内原理验证，循环应用这一策略是药物发现领域的关键挑战。通过在药物发现中采用更复杂且更具信息量的模型，影像技术可提升临床前癌症研究的真实性与统计稳健性。本综述重点阐述，将先进影像与三维体系及活体小鼠模型相结合，如何为癌症药物发现提供更富信息且贴近疾病的平台。

原文链接：

Developments in preclinical cancer imaging: innovating the discovery of therapeutics