CNS Lymphoma

Hyperpolarized imaging can monitor treatment response in lymphoma murine models

NF-kB is a key pro-survival transcriptional regulator that drives resistance in a variety of malignancies, one of which is primary CNS lymphoma (PCNSL) a highly refractory form of activated B-cell (ABC)-type large cell lymphoma. ABC-type large cell lymphomas are an important cause of cancer-related mortality worldwide. Recent clinical trials using targeted agents that block NF-kB activation have shown activity, in both PCNSL as well as in systemic ABC-type lymphoma, yet responses generally last 2-4 months, suggesting that alternative pathways of NF-kB activation are adaptively induced to mediate resistance.

In this research conducted inpartnership with our co-PI Prof. James Rubenstein and his team, we will explore the potential of hyperpolarized 13C MRI to detect target inhibition in PCNSL, and if this strategy could be used to identify effective combinatorial strategies that durably suppress NF-kB activation. In addition, we envision that this approach may be impactful in identifying biomarkers that predict efficacy of immunotherapeutic strategies. Our team and colleagues at UCSF recently demonstrated for the first time the feasibility of HP 13C MRI to image human brain and malignant glioma in patients. Results of these studies support the potential of HP 13C MRI to identify metabolites that yield impactful non-invasive biomarkers of in vivo metabolic processes in PCNSL, including resistance pathways, with markedly improved sensitivity and specificity compared to standard MRI and thus facilitate precision medicine.