# Application of Hyperpolarized 13C Magnetic Resonance Imaging to Detect Target Inhibition of NF-kB Activation and Response in Primary CNS Lymphoma

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $613,413

## Abstract

PROJECT SUMMARY/ABSTRACT
This proposal will apply an innovative metabolic imaging approach, hyperpolarized (HP) 1-13-C MRI to address
NF-kB activation in cancer. 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 trials using targeted agents that block NF-kB activation have shown activity in
PCNSL and systemic ABC-type lymphoma, yet responses last only a few months, suggesting that alternative
pathways of NF-kB activation are adaptively induced to mediate resistance. We hypothesize that HP 1-13-C
MRI may have particular utility in detecting clinical response, defining prognosis and target inhibition in PCNSL
and can also be applied 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
immunotherapy. Our team recently demonstrated for the first time the feasibility of HP 1-13-C MRI to image
malignant glioma in patients. These studies support the potential of HP 1-13-C 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. We have recruited a talented,
multidisciplinary team to pursue this highly translational project to address key gaps in PCNSL research through
pursuit of the following specific Aims:
1) Test the hypothesis that hyperpolarized (HP) [1-13-C]-metabolic MR imaging of genetically-defined, patient-
derived orthotopic models of PCNSL can non-invasively evaluate depth of response to combinations of NF-kB
targeting agents as well as provide an early biomarker of the emergence of resistance.
2) Test the hypothesis that HP [1-13-C] metabolic MR metrics can be developed as non-invasive biomarkers of
NF-kB-activation and immunosuppression in a syngeneic, immunocompetent model of PCNSL.
3) Perform the initial proof of principle patient studies of HP 13C MRI to determine feasibility and methods of HP
[1-13C] pyruvate MRI as a real time, non-invasive imaging tool for response assessment in PCNSL.
We will correlate genetic markers of NF-kB activation in tumors with lactate on HP 13C MRI and lactate in
cerebrospinal fluid and their relationship to progression-free survival. These studies will constitute a basis for
integration of HP13C metabolic imaging in the research of PCNSL, and of ABC-type lymphomas in general, to
improve detection, prognostication, identify resistance, and facilitate precision medicine. We anticipate these
studies will identify novel combinations and schedules of agents that durably block NF-kB, to be tested in the
clinic. These studies may also p...

## Key facts

- **NIH application ID:** 10177970
- **Project number:** 5R01CA239462-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Myriam Marianne Chaumeil
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $613,413
- **Award type:** 5
- **Project period:** 2019-07-04 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10177970

## Citation

> US National Institutes of Health, RePORTER application 10177970, Application of Hyperpolarized 13C Magnetic Resonance Imaging to Detect Target Inhibition of NF-kB Activation and Response in Primary CNS Lymphoma (5R01CA239462-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10177970. Licensed CC0.

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