Multimodal imaging in an experimental rat model for brain metastasis (EMIM, 2017)

Authors: Valerie De Meulenaere1, Christian Vanhove2, Sara Neyt3, Bert Vandeghinste3, Pieter Mollet3, Elke Decrock4, Olivier De Wever5, Benedicte Descamps2, Karel Deblaere1

Affiliations

  1. Department of Radiology and Nuclear Medicine, Ghent University, Ghent, Belgium.
  2. IBiTech – MEDISIP – INFINITY, Ghent University, Belgium.
  3. MOLECUBES NV, Ghent Belgium.
  4. Department of Basic Medical Sciences, Ghent University, Ghent, Belgium.
  5. Department of Experimental Cancer Research, Ghent University, Ghent, Belgium.

Introduction

Metastatic brain tumors are a severe problem in the treatment of patients with breast carcinoma. We developed a rat model for brain metastasis that allows follow-up by MRI. Injection of cancer cells labeled with iron oxide particles, allows tracking from the single-cell stage until the appearance of full-blown metastases.

Methods

MDA-MB-231br/eGFP human breast cancer cells were labeled with micron-sized particles of iron oxide (MPIO; 1μm). 13 female immunodeficient rats were intracardially injected with 100.000 labeled cells at the age of 5 weeks (1). MRI was performed on a 7T system (PharmaScan) at day 1, and then weekly until 10 weeks post-injection. T2*W images were acquired one day post-injection to show the initial distribution of MPIO-labeled cells in the brain. T2W sequences were acquired to visualize the brain metastases. A static whole-body 18F-FDG PET-CT (bèta-CUBE, MOLECUBES NV, 10 MBq, 30 minutes acquisition) was performed to determine metastasis development outside the brain. For detection of bone metastases full body spiral high-resolution CT acquisitions were performed (X-CUBE, MOLECUBES NV, 7 minutes acquisition).

Results

At week 3 to 4 the first signs of brain metastasis development were visible as hyperintensities on T2W images in all animals. The metastases visible on T2W images could be correlated to their corresponding hypointensities on T2*W images. Whole-body PET imaging suggested hot spots in the lungs of 2 animals. Cellular alterations in the lung were confirmed with haematoxylin and eosin staining. Bone metastases were detected in 11 out of 13 animals with CT evaluation.

Conclusions

Our aim was to develop a rat model for brain metastasis. However, early formation of metastases outside the brain was observed in the lungs and bone, as evidenced by PET and CT, respectively. This indicates that this model is currently not suited for investigating brain metastasis and associated treatment strategies. Therefore, the brain metastatic propensity of the cell line will be optimized by in vivo passaging.

References

  1. Yoneda et al. J Bone Mineret al.Res 2001 16, 1486–1495.
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