Abstract
PurposeMetastatic brain tumors pose a severe problem in the treatment of patients with breast carcinoma. 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).ProceduresGreen 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 initial distribution of MPIO-labeled cancer cells and to visualize metastasis in the brain. Occurrence 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.ResultsThe first signs of brain metastasis development were visible as hyperintensities on T2-weighted (T2w) MR images 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.ConclusionsOur 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.
Highlights
Tumor metastasis is the leading cause of cancer death worldwide
The first signs of brain metastasis development were visible as hyperintensities on T2weighted (T2w) MR images acquired 3 weeks after intracardiac injection in rats and mice
Almost no bone metastasis development was observed in mice after positron emission tomography (PET)/ computed tomography (CT) evaluation
Summary
Tumor metastasis is the leading cause of cancer death worldwide. Breast carcinomas frequently metastasize to the brain with brain metastasis occurring in up to 10–15% of breast cancer patients with metastatic disease [1]. Orthotopic implantation of primary tumors that metastasize spontaneously often leads to systemic disease and death of the animals before the brain can be reliably examined [4]. To avoid passage of cancer cells into the pulmonary system, intracardiac injection into the left ventricle of the heart can be an alternative. This type of injection leads to a systemic distribution of the cancer cells to most organs [5]. The experimental brain metastasis model should closely mimic human disease so intracardiac injection is the most preferable method to induce metastasis in the brain
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