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Species-dependent extracranial manifestations of a brain seeking breast cancer cell line

Valerie De Meulenaere, Sara Neyt, Bert Vandeghinste, Pieter Mollet, Olivier De Wever, Elke Decrock, Luc Leybaert, Ingeborg Goethals, Christian Vanhove, Benedicte Descamps, Karel Deblaere
Purpose Metastatic brain tumors pose a severe problem in the treatment of patients with breast carci- noma. Preclinical models have been shown to play an important role in unraveling the underlying mechanisms behind the metastatic process and evaluation of new therapeutic approaches. As the size of the rat brain allows improved in vivo imaging, we attempted to establish a rat model for breast cancer brain metastasis that allows follow-up by 7 tesla (7T) preclinical Magnetic Resonance Imaging (MRI). Procedures Green fluorescent protein-transduced (eGFP) MDA-MB-231br breast cancer cells were labeled with micron-sized particles of iron oxide (MPIOs) and intracardially injected in the left ventricle of female nude rats and mice. 7T preclinical MRI was performed to show the ini- tial distribution of MPIO-labeled cancer cells and to visualize metastasis in the brain. Occur- rence of potential metastasis outside the brain was evaluated by 2-deoxy-2-[18F]fluoro-D- glucose ([18F]FDG) positron emission tomography (PET)/computed tomography (CT) and potential bone lesions were assessed using [18F]sodium fluoride ([18F]NaF) PET/CT. Results The first signs of brain metastasis development were visible as hyperintensities on T2- weighted (T2w)MRimages acquired 3 weeks after intracardiac injection in rats and mice. Early formation of unexpected bone metastasis in rats was clinically observed and assessed using PET/CT. Almost no bone metastasis development was observed in mice after PET/ CT evaluation. Conclusions Our results suggest that the metastatic propensity of the MDA-MB-231br/eGFP cancer cell line outside the brain is species-dependent. Because of early and abundant formation of bone metastasis with the MDA-MB-231br/eGFP cancer cell line, this rat model is currently not suitable for investigating brain metastasis as a single disease model nor for evaluation of novel brain metastasis treatment strategies.

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