文章：

临床前肿瘤模型成像：提高翻译能力

Imaging preclinical tumour models: improving translational power

原文发布日期：2014-06-19

DOI: 10.1038/nrc3751

类型: Review Article

开放获取: 否

要点：

1. Small-animal imaging in cancer research is a dynamic research field, with tremendous progress that has resulted from substantial developments in small-animal imaging techniques, specific imaging probes and advances in innovative animal tumour models.
2. Multimodal small-animal imaging techniques provide complementary and therefore more complete information (as one technique can compensate for the weaker characteristics of others).
3. Molecular imaging probes can be applied for many different purposes in cancer research, including visualization of tumour cell and extracellular matrix characteristics, diagnosis, staging, therapy selection, therapy and monitoring of therapy response.
4. Well-defined model systems and study designs are needed to bridge the gap between oncological in vitro studies and clinical application. Two stages in the translation of in vitro results can be distinguished: the first step comprises translation from the laboratory bench to animal models, the second step involves translation from animal models to the clinic. Research questions related to each stage ask for different models and matching imaging techniques to get the most reliable answers.
5. Increased knowledge of cancer type-specific genes has supported the generation of genetically engineered mouse models that capture both the cell-intrinsic and cell-extrinsic factors that drive organ-specific cancer development and the progression towards metastatic disease.
6. 'Close to patient' models, such as patient-derived xenografts and reconstituted 'humanized' xenografts, as well as patient-derived ex vivo organoid three-dimensional cultures and tissue-slice systems, aim to capture the unique patient-specific tumour microenvironment and to sustain tumour heterogeneity.
7. Careful selection of the most appropriate model system and best (multimodal) imaging modalities, as well as an optimal study design, are crucial decision points that determine the translational impact of the study.
8. Close collaboration of different disciplines, specific training of preclinical and basic researchers, harmonization of protocols and stricter publication guidelines are needed and will help to further improve the translation of results from the small-animal imaging research field into the clinic.

要点翻译：

1. 癌症研究中的小动物成像是一个动态的研究领域，其巨大进展源于小动物成像技术、特异性成像探针以及创新性动物肿瘤模型发展的重大突破。
2. 多模态小动物成像技术可提供互补性信息，从而获得更完整的数据（因为一种技术能够弥补其他技术的局限性）。
3. 分子成像探针在癌症研究中具有多种应用场景，包括肿瘤细胞与细胞外基质特性可视化、诊断、分期、治疗方案选择、治疗实施及疗效监测。
4. 需要建立明确的模型系统与研究设计，以填补肿瘤学体外研究与临床应用之间的鸿沟。体外研究结果的转化可分为两个阶段：第一阶段涉及从实验室向动物模型的转化，第二阶段涵盖从动物模型向临床的转化。针对不同阶段的研究问题需要采用差异化模型与匹配的成像技术，以获取最可靠的答案。
5. 对癌症类型特异性基因的深入认识促进了基因工程小鼠模型的构建，这类模型能同时捕捉驱动器官特异性癌症发展及转移进程的细胞内在因素与细胞外在因素。
6. "贴近临床"的模型（如患者来源的异种移植模型、重建的"人源化"异种移植模型）以及患者来源的离体类器官三维培养体系和组织切片系统，旨在保留患者特异性肿瘤微环境的独特性并维持肿瘤异质性。
7. 精准选择最适宜的模型系统与最优（多模态）成像方案，以及制定完善的研究设计，是决定研究成果转化价值的关键决策点。
8. 需要加强跨学科紧密合作、开展临床前基础研究人员的专项培训、推动实验方案的标准化并实施更严格的论文发表规范，这些举措将有力促进小动物成像领域研究成果向临床应用的转化。

英文摘要：

Recent developments and improvements of multimodal imaging methods for use in animal research have substantially strengthened the options of in vivo visualization of cancer-related processes over time. Moreover, technological developments in probe synthesis and labelling have resulted in imaging probes with the potential for basic research, as well as for translational and clinical applications. In addition, more sophisticated cancer models are available to address cancer-related research questions. This Review gives an overview of developments in these three fields, with a focus on imaging approaches in animal cancer models and how these can help the translation of new therapies into the clinic.

摘要翻译： 

近期，用于动物研究的多模态成像方法的发展与改进，显著增强了在体可视化癌症相关过程的能力。此外，探针合成与标记技术的进步，已催生出既适用于基础研究，也具有转化及临床应用潜力的成像探针。同时，更多精细的癌症模型可供解答癌症相关的研究问题。本综述概述了这三个领域的进展，重点聚焦于动物癌症模型中的成像方法，以及这些方法如何促进新疗法向临床的转化。

原文链接：

Imaging preclinical tumour models: improving translational power