Abstract
Rapid diagnosis and therapeutic monitoring of aggressive diseases such as glioblastoma can improve patient survival by providing physicians the time to optimally deliver treatment. This research tested whether metabolic imaging with hyperpolarized MRI could detect changes in tumor progression faster than conventional anatomic MRI in patient-derived glioblastoma murine models. To capture the dynamic nature of cancer metabolism, hyperpolarized MRI, NMR spectroscopy, and immunohistochemistry were performed at several time-points during tumor development, regression, and recurrence. Hyperpolarized MRI detected significant changes of metabolism throughout tumor progression whereas conventional MRI was less sensitive. This was accompanied by aberrations in amino acid and phospholipid lipid metabolism and MCT1 expression. Hyperpolarized MRI can help address clinical challenges such as identifying malignant disease prior to aggressive growth, differentiating pseudoprogression from true progression, and predicting relapse. The individual evolution of these metabolic assays as well as their correlations with one another provides context for further academic research.
Highlights
The radiotherapy dose of 2 × 5 Gy was effective at extending the survival of tumor-bearing mice, allowing for tumor regression and recurrence to be assessed in the radiotherapy treated mouse cohort
Our findings demonstrate that in situ analysis of metabolic changes linking the stages of tumor progression using hyperpolarized MRI and nuclear magnetic resonance (NMR) spectroscopy is feasible and informative
This study demonstrated and discussed the benefits that hyperpolarized MRS could add to conventional clinical imaging to address several clinical challenges in the diagnosis and treatment of GBM. These include the ability to predict whether a tumor will be slowgrowing or aggressive at the time of diagnosis, help discriminate pseudoprogression from true progression and predict whether patient survival will be improved shortly after administration of a treatment, and determine whether the patient is on the verge of relapse during a follow-up exam
Summary
Despite standard-of-care treatment with surgery, radiotherapy, and temozolomide chemotherapy, prevailing therapies remain palliative, and tumors are almost always recurrent and lead to median survival times of approximately 15 months [2]. Alternative therapies, both FDA-approved and experimental, have shown little to no improvement on overall survival, as factors such as relatively average mutational load, tumor heterogeneity, and molecular filtration by the blood-brain barrier challenge drug development for this disease [3]. This failure to make major inroads points to the need for alternative approaches in the management of this disease
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