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The use of alginate based microcapsules to deliver drugs and cells with a minimal host interaction is increasingly being proposed. A proficient method to track the position of the microcapsules during such therapies, particularly if they are amenable to commonly used instrumentation, would greatly help the development of such treatments. Here we propose to label the microcapsules with gold nanoparticles to provide a bright contrast on small animal x-ray micro-CT systems enabling single microcapsule detection. The microcapsules preparation is based on a simple protocol using inexpensive compounds. This, combined with the widespread availability of micro-CT apparatus, renders our method more accessible compared with other methods. Our labeled microcapsules showed good mechanical stability and low cytotoxicity in-vitro. Our post-mortem rodent model data strongly suggest that the high signal intensity generated by the labeled microcapsules permits the use of a reduced radiation dose yielding a method fully compatible with longitudinal in-vivo studies., From the Clinical Editor: The authors of this study report the development of a micro-CT based tracking method of alginate-based microcapsules by incorporating gold nanoparticles in the microcapsules. They demonstrate the feasibility of this system in rodent models, where due to the high signal intensity, even reduced radiation dose is sufficient to track these particles, providing a simple and effective method to track these commonly used microcapsules and allowing longitudinal studies., (Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.)

In the present study complementary high-resolution imaging techniques on different length scales are applied to elucidate a cellular loading protocol of gold nanoparticles and subsequently its impact on long term and high-resolution cell-tracking utilizing X-ray technology. Although demonstrated for malignant cell lines the results can be applied to non-malignant cell lines as well. In particular the accumulation of the gold marker per cell has been assessed quantitatively by virtue of electron microscopy, two-dimensional X-ray fluorescence imaging techniques and X-ray CT with micrometric and sub-micrometric resolution. Moreover, utilizing these techniques the three dimensional distribution of the incorporated nanoparticles, which are sequestered in lysosomes as a permanent marker, could be determined. The latter allowed elucidation of the gold partition during mitosis and the cell size, which subsequently enabled us to define the optimal instrument settings of a compact microCT system to visualize gold loaded cells. The results obtained demonstrate the feasibility of cell-tracking using X-ray CT with compact sources.

The ability to perform cell tracking using x-ray computed tomography combined with gold nanoparticles has been demonstrated recently on ex vivo samples using different malignant and nonmalignant cell lines. Here we proved the concept of the method for in vivo assessment in a small-animal model of malignant brain tumors. The limitations of the method due to radiation dose constraints were investigated using Monte Carlo simulations. Taking into consideration different x-ray entrance doses and the spatial resolution, the visibility of the cell clusters was evaluated. The results of the experiments conducted on mice implanted with F98 tumor cells confirmed the prediction of the Monte Carlo calculations. Small clusters of cells exogenously loaded with gold nanoparticles could be visualized using our in vivo method., From the Clinical Editor: This article discusses the use of CT-based detection of gold nanoparticle loaded cells of interest in small-animal models of malignant brain tumors, where small clusters of cells loaded with gold nanoparticles could be visualized., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The ability to track cells in small-animal models of human disease is important because it gives the potential to improve our understanding of the processes of disease progression as well as our understanding of the therapeutic effects of interventions. In this study gold nanoparticles have been used as a permanent marker of implanted normal and malignant cell grafts in combination with a suitable x-ray apparatus. Using x-ray computed tomography the micrometric three-dimensional distribution of these marked cells could be displayed with penetration depth, high cell sensitivity and high spatial resolution in rodent models of human diseases. In principle the method allows quantification of cell numbers at any anatomical location over time in small animals., (Copyright © 2011 Elsevier Inc. All rights reserved.)

In the present study, the in vivo distribution of polyelectrolyte multilayer coated gold nanoparticles is shown, starting from the living animal down to cellular level. The coating was designed with functional moieties to serve as a potential nano drug for prion disease. With near infrared time-domain imaging we followed the biodistribution in mice up to 7 days after intravenous injection of the nanoparticles. The peak concentration in the head of mice was detected between 19 and 24 h. The precise particle distribution in the brain was studied ex vivo by X-ray microtomography, confocal laser and fluorescence microscopy. We found that the particles mainly accumulate in the hippocampus, thalamus, hypothalamus, and the cerebral cortex.