Glioblastoma multiforme (GBM) (also called glioblastoma) is a fast-growing glioma that develops from star-shaped glial cells (astrocytes and oligodendrocytes) that support the health of the nerve cells within the brain. These tumors are usually highly malignant because the cells reproduce quickly and they are supported by a large network of blood vessels. GBM is the most common and most aggressive form of malignant primary brain tumors, affecting nearly 23,000 people in the United States annually. Most preclinical studies in glioma utilize survival as the primary endpoint, which provides limited information about disease progression or primary tumor response to treatment.
Covance has characterized approximately 20 human and murine glioma cell lines. About half of these glioma cell lines have been modified to express luciferase in order to enable in vivo optical monitoring using bioluminescence imaging (BLI). BLI allows for the detection of light from a small number of live luciferase-enable cells. Therefore staging and pair-wise distribution of animals can occur when the tumor burden is relatively small. The ability to stage and start treatment early is an advantage of bioluminescence imaging. The limitation of this imaging modality is determining exact location and circumference of the tumor; BLI measures light emitted from the cell and cannot account for depth or placement. In order to accurately determine tumor burden, anatomical magnetic resonance imaging (MRI) is required. Anatomical MRI has the ability to precisely measure tumors at ~2mm3. MRI’s much higher resolution (~100µm), not only measures total tumor burden but can provide specific tumor location coordinates. The correlation of tumor burden as determined by anatomical MRI and BLI was very high for all of the orthotopic GBM models we have evaluated.
Fig. 1: BLI/MRI Image Time Course – U87-MG-luc Intracranial Orthotopic Implant, 106 cells/mouse
As an example, the U87MG-luc human glioblastoma/astrocytoma is a highly utilized and published preclinical model. Covance has completed over 40 orthotopic in vivo studies with the U87MG line (parental and luciferase-enabled). This model has proven to be reliable and reproducible. In an effort to further characterize the model, Molecular Imaging has evaluated the standard growth with both anatomical MRI and BLI. The correlation between the tumor burden assessed by anatomical MRI and BLI is very high. Please see Figures 1 and 2 with regards to this data.
Fig. 2: Tumor Burden Quantification BLI (total luciferase signal) vs MRI (T2w tumor volume)
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Note: Studies were performed in accordance with applicable animal welfare regulations in an AAALAC-accredited facility