Research Article
In vivo visualization of gold-loaded cells in mice using x-ray computed tomography

https://doi.org/10.1016/j.nano.2012.06.004Get rights and content

Abstract

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.

Graphical Abstract

Gold nanoparticles (GNPs) are conjugated with horse serum proteins to induce cellular uptake. F98 glioma cells are loaded with GNPs and then injected into mouse brains. One week after tumor cell implantation the tumor has grown and the concentration of the GNP marker has decreased. In vivo x-ray CT was used to measure the tumor volume and to follow its growth by measuring the x-ray attenuation.

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Section snippets

Methods

All animal experiments were carried out in accordance with the German and Italian guidelines for animal research. Permission to conduct the experiment was obtained in both countries.

Simulation

As an example, Figure 1, B shows a reconstructed slice of the simulated tumor, comprising an estimated 62,500 ± 4000 cells after two cell divisions. The ESD was 160 mGy using the discrete 3D head model as depicted in Figure 1, A. The pixel value is the linear attenuation coefficient. On the chosen gray scale, white would represent 3.15 cm–1 (4894 HU) and the black shade 5.6 × 10–4 cm–1 (–1000 HU). In this example the SNR = 66 and the C = 1.58 for an ROI that includes 88 pixels/voxel. A

Discussion

By means of a Monte Carlo simulation we were able to optimize the x-ray imaging protocol in terms of pixel size, exposure time, and entrance dose for in vivo cell tracking in a mouse model of human glioblastoma multiforme. From our simulations it turned out that quantitative volume evaluation of tumors based on GNP-loaded cells that had undergone two cell divisions could be considered compatible with an in vivo CT scan with no adverse effects on the animals’ health. The ESD for this

Acknowledgments

The authors are indebted to Diego Dreossi, Nicola Sodini, and Lucia Mancini for the help at the SYRMEP beamline.

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