Theranostics 2020; 10(4):1884-1909. doi:10.7150/thno.38625


Spatial heterogeneity of nanomedicine investigated by multiscale imaging of the drug, the nanoparticle and the tumour environment

Josanne Sophia de Maar1, Alexandros Marios Sofias2, Tiffany Porta Siegel3, Rob J. Vreeken3,4, Chrit Moonen1, Clemens Bos1, Roel Deckers1✉

1. Division of Imaging and Oncology, University Medical Center Utrecht, Utrecht University, the Netherlands.
2. Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
3. The Maastricht Multimodal Molecular Imaging Institute (M4I), Division of Imaging Mass Spectrometry, Maastricht University, Maastricht, the Netherlands.
4. Janssen Research & Development, Beerse, Belgium.

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de Maar JS, Sofias AM, Porta Siegel T, Vreeken RJ, Moonen C, Bos C, Deckers R. Spatial heterogeneity of nanomedicine investigated by multiscale imaging of the drug, the nanoparticle and the tumour environment. Theranostics 2020; 10(4):1884-1909. doi:10.7150/thno.38625. Available from

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Genetic and phenotypic tumour heterogeneity is an important cause of therapy resistance. Moreover, non-uniform spatial drug distribution in cancer treatment may cause pseudo-resistance, meaning that a treatment is ineffective because the drug does not reach its target at sufficient concentrations. Together with tumour heterogeneity, non-uniform drug distribution causes “therapy heterogeneity”: a spatially heterogeneous treatment effect. Spatial heterogeneity in drug distribution occurs on all scales ranging from interpatient differences to intratumour differences on tissue or cellular scale. Nanomedicine aims to improve the balance between efficacy and safety of drugs by targeting drug-loaded nanoparticles specifically to tumours. Spatial heterogeneity in nanoparticle and payload distribution could be an important factor that limits their efficacy in patients. Therefore, imaging spatial nanoparticle distribution and imaging the tumour environment giving rise to this distribution could help understand (lack of) clinical success of nanomedicine. Imaging the nanoparticle, drug and tumour environment can lead to improvements of new nanotherapies, increase understanding of underlying mechanisms of heterogeneous distribution, facilitate patient selection for nanotherapies and help assess the effect of treatments that aim to reduce heterogeneity in nanoparticle distribution.

In this review, we discuss three groups of imaging modalities applied in nanomedicine research: non-invasive clinical imaging methods (nuclear imaging, MRI, CT, ultrasound), optical imaging and mass spectrometry imaging. Because each imaging modality provides information at a different scale and has its own strengths and weaknesses, choosing wisely and combining modalities will lead to a wealth of information that will help bring nanomedicine forward.

Keywords: Drug distribution, Nanomedicine, Clinical Imaging, Optical imaging, Mass Spectrometry Imaging.