Imaging preclinical tumour models: improving translational power

Key Points

  • 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.

  • Multimodal small-animal imaging techniques provide complementary and therefore more complete information (as one technique can compensate for the weaker characteristics of others).

  • 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.

  • 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.

  • 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.

  • '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.

  • 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.

  • 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.

Abstract

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.

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Figure 1: Model systems and main imaging techniques for translation from in vitro analysis to clinical implementation.
Figure 2: Overview of various types of currently commercially available in vivo molecular multimodal imaging systems and applications.
Figure 3: Schematic representation of molecular imaging targets in tumour cells and the general structure of imaging probes.
Figure 4: Alternative models for molecular imaging.

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Acknowledgements

The authors thank the members of their laboratories for their critical comments and helpful discussions. The authors thank the biotechnicians in the groups for many years of dedicated work 'behind the scenes' to propagate precious PDX models valuable to many research projects, as well as for the many imaging studies performed; the authors thank the SPECTRIM group at Erasmus MC, The Netherlands, for providing Figures 2a and 2b. The authors apologize to those whose work is not cited owing to space limitations. Part of the authors' research is funded by Erasmus MC grants, grants from the SUWO (Stichting Urologisch Wetenschappelijk Onderzoek), from the Innovative Medicines Initiative (IMI) Joint Undertaking ('PREDECT', grant agreement number 115188) by EU FP7 and EFPIA companies, a grant from the 'Lijf en Leven' foundation ('DIVERS'), equipment grants (91111012 and 91105015) from the Dutch Organization of Scientific Research (NWO), a grant from the Dutch Cancer Society (KWF; EMCR 2008-4037) and a grant from EU FP7 ITN PITN-GA-2012-317019.

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de Jong, M., Essers, J. & van Weerden, W. Imaging preclinical tumour models: improving translational power. Nat Rev Cancer 14, 481–493 (2014). https://doi.org/10.1038/nrc3751

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