Hyperpolarized MRI for CNS Lymphoma

Overseen By Wendy Ma

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: James Rubenstein

Must be taking: Methotrexate, Temozolomide, Rituximab

Disqualifiers: Congestive heart failure, Other cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: Up to 4 months

25 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are in Cohort 2, you will receive specific treatments like high-dose methotrexate, temozolomide, and rituximab.

What data supports the effectiveness of the treatment Hyperpolarized 13C pyruvate MRI for CNS Lymphoma?

Research shows that Hyperpolarized 13C pyruvate MRI can track tumor metabolism and detect treatment responses in brain tumors, as seen in studies with glioma models and pediatric brain tumors. This suggests it could be useful for evaluating CNS lymphoma by providing detailed metabolic information and early detection of treatment effects. ^{1 2 3 4 5}

Is hyperpolarized 13C pyruvate MRI safe for humans?

Hyperpolarized 13C pyruvate MRI has been used safely in clinical studies, including imaging in healthy human volunteers, without the use of ionizing radiation, suggesting it is generally safe for humans. ^{1 2 3 4 6}

How is the treatment Hyperpolarized pyruvate (13C) unique for CNS Lymphoma?

Hyperpolarized pyruvate (13C) is unique because it allows for real-time imaging of tumor metabolism using MRI, providing detailed insights into how the tumor processes energy. This approach is different from traditional treatments as it offers a non-invasive way to monitor tumor activity and response to therapy, potentially leading to more personalized treatment plans. ^{2 3 4 5 7}

What is the purpose of this trial?

This phase I trial evaluates the feasibility of using hyperpolarized carbon C 13 pyruvate magnetic resonance imaging (MRI) in diagnosing patients with primary central nervous system lymphoma. This trial aims to see whether MRI using hyperpolarized carbon-13 pyruvate is safe and useful for detecting central nervous system lymphoma and evaluating response to treatment.

Research Team

James Rubenstein, MD, PhD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

This trial is for adults over 18 with primary central nervous system lymphoma, who have a life expectancy of more than 12 weeks. They must have measurable disease on MRI and adequate kidney function. It's not for those with significant medical illnesses, heart failure, other cancers within the last 3 years (except certain skin cancers or cervical carcinoma in-situ), pregnant or breastfeeding women, or anyone unable to follow study procedures.

Inclusion Criteria

Each participant must sign an institutional review board-approved informed consent document in accordance with federal and institutional guidelines. Patients must sign an authorization for release of their protected health information.

I have a confirmed primary CNS lymphoma with a lesion over 1cm visible on MRI.

My cancer is a type of non-Hodgkin lymphoma in the brain.

Exclusion Criteria

Subjects must be excluded from participating in this study if are not able to comply with study and/or follow-up procedures.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Imaging

Participants receive hyperpolarized carbon C 13 pyruvate intravenously and undergo MRI at baseline

1 day

1 visit (in-person)

Treatment

Participants in Cohort 2 receive standard high-dose methotrexate, temozolomide plus rituximab therapy, followed by MRI imaging

Up to 4 months

Multiple visits (in-person) for chemotherapy and imaging

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up every 3 months for 2 years, every 6 months for the next 3 years, and then annually for the next 5 years

Up to 10 years

Regular follow-up visits

Treatment Details

Interventions

• Hyperpolarized pyruvate (13C)
• Magnetic resonance imaging (MRI)

Trial Overview The trial is testing the safety and usefulness of a new type of MRI that uses hyperpolarized carbon C 13 pyruvate to diagnose CNS lymphoma and monitor treatment response. Participants will undergo this special imaging to see if it provides clear pictures of their condition.

Participant Groups

Group I: Cohort 2: Hyperpolarized pyruvate (13C) Experimental Treatment 2 Interventions

Newly diagnosed PCNSL participants with planned treatment of standard high-dose methotrexate,temozolomide plus rituximab (MT-R) regimen will receive hyperpolarized carbon C 13 pyruvate intravenously (IV) and undergo MRI at baseline and again after three cycles of of standard induction chemotherapy. An optional second HP 13C pyruvate injection and MRI acquisition will be offered on same day following completion of the first scan. Participants in Cohort 2 will also have option to undergo an additional imaging at a later time if the participant's cancer progresses.

Group II: Cohort 1: Hyperpolarized pyruvate (13C) Experimental Treatment 2 Interventions

Histologically proven relapsed PCNSL patients will receive hyperpolarized carbon C 13 pyruvate intravenously (IV) and undergo MRI at baseline. An optional second HP 13C pyruvate injection and MRI acquisition will be offered on same day following completion of the first scan.

Who Is Running the Clinical Trial?

James Rubenstein

Lead Sponsor

Trials

3

Recruited

70+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Hyperpolarized [1-(13)C]pyruvate can effectively detect treatment responses in glioma tumors, which is challenging with traditional imaging methods like PET due to interference from normal brain tissue signals.

In a rat model, significant lactate labeling was observed in glioma tumors after treatment, with a notable decrease in the ratio of tumor lactate to blood pyruvate signal following whole brain irradiation, indicating a potential response to therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detecting response of rat C6 glioma tumors to radiotherapy using hyperpolarized [1- 13C]pyruvate and 13C magnetic resonance spectroscopic imaging. Day, SE., Kettunen, MI., Cherukuri, MK., et al.[2021]

This study successfully used MR spectroscopic imaging of hyperpolarized [2-(13)C]pyruvate to visualize metabolic changes in glioma-bearing rat brains, revealing higher lactate and lower glutamate levels in tumors compared to normal brain tissue.

Administration of dichloroacetate increased glutamate levels in both tumor and normal brain tissue, indicating its potential to modulate mitochondrial metabolism in gliomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Volumetric spiral chemical shift imaging of hyperpolarized [2-(13) c]pyruvate in a rat c6 glioma model. Park, JM., Josan, S., Jang, T., et al.[2018]

Hyperpolarized 13C-MRI, which enhances the detection of tumor metabolism by 4-5 orders of magnitude, can track the metabolism of hyperpolarized [1-13C]pyruvate in cancer patients, providing insights into tumor activity and response to treatment.

Combining HP 13C-MRI with traditional 1H-MRI allows for detailed anatomical imaging and functional tumor analysis, potentially enabling early identification of patients who are not responding to therapies, although cost and technical challenges need to be addressed for broader clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperpolarized Carbon-13 MRI in Breast Cancer. Woitek, R., Brindle, KM.[2023]

This study is the first to use hyperpolarized 13C MRI to visualize and measure how the human brain processes [2-13C]pyruvate, providing insights into cerebral energy metabolism.

In a trial involving 5 healthy volunteers, the technique allowed for the simultaneous assessment of glycolytic and oxidative metabolism by quantifying the conversion rates of pyruvate to lactate and glutamate, highlighting its potential for advanced metabolic imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperpolarized [2-13C]pyruvate MR molecular imaging with whole brain coverage. Chung, BT., Kim, Y., Gordon, JW., et al.[2023]

The study demonstrated that hyperpolarized carbon-13 (HP-13C) metabolic imaging is safe and well-tolerated in pediatric patients with brain tumors, with no adverse events reported during the imaging process.

HP-13C imaging successfully showed the brain's metabolism of HP [1-13C]pyruvate, indicating its potential as a useful tool for assessing metabolic changes in pediatric CNS tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot Study of Hyperpolarized 13C Metabolic Imaging in Pediatric Patients with Diffuse Intrinsic Pontine Glioma and Other CNS Cancers. Autry, AW., Park, I., Kline, C., et al.[2022]

Hyperpolarized 13C magnetic resonance spectroscopic (MRS) imaging, particularly using [1-13C]pyruvate, allows for non-invasive real-time detection of metabolic processes, such as lactate and bicarbonate production, without ionizing radiation.

This technique has shown potential in clinical studies for assessing metabolic changes in conditions like cancer and heart ischemia, indicating its future role in advanced metabolic imaging despite needing further technical improvements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperpolarized MRI - An Update and Future Perspectives. Jørgensen, SH., Bøgh, N., Hansen, E., et al.[2022]

Hyperpolarized MRI using [1-13C] pyruvate can effectively characterize energy metabolism in the human brain and identify altered cancer metabolism in brain tumors, as evidenced by the production of HP lactate from HP pyruvate.

This method shows promise as a quantitative metabolic biomarker for assessing tumor response, correlating well with standard clinical imaging techniques like MRI and PET/CT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolic Imaging of the Human Brain with Hyperpolarized 13C Pyruvate Demonstrates 13C Lactate Production in Brain Tumor Patients. Miloushev, VZ., Granlund, KL., Boltyanskiy, R., et al.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Detecting response of rat C6 glioma tumors to radiotherapy using hyperpolarized [1- 13C]pyruvate and 13C magnetic resonance spectroscopic imaging. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Volumetric spiral chemical shift imaging of hyperpolarized [2-(13) c]pyruvate in a rat c6 glioma model. [2018]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Hyperpolarized Carbon-13 MRI in Breast Cancer. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Hyperpolarized [2-13C]pyruvate MR molecular imaging with whole brain coverage. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Pilot Study of Hyperpolarized 13C Metabolic Imaging in Pediatric Patients with Diffuse Intrinsic Pontine Glioma and Other CNS Cancers. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Hyperpolarized MRI - An Update and Future Perspectives. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Metabolic Imaging of the Human Brain with Hyperpolarized 13C Pyruvate Demonstrates 13C Lactate Production in Brain Tumor Patients. [2019]