Hyperpolarized C 13 Pyruvate Imaging for Brain Cancer

Overseen By Dawid Schellingerhout

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: Pacemakers, Metallic implants, Pregnancy, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 1 day

13 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial studies how an imaging agent, hyperpolarized carbon C 13 pyruvate, works in diagnosing glioma in patients with brain tumors. Giving hyperpolarized carbon C 13 pyruvate before an advanced imaging technique called a magnetic resonance spectroscopic imaging (MRSI) scan may help researchers better diagnose glioma in patients with brain tumors.

Do I need to stop my current medications to participate in the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Hyperpolarized Carbon C 13 Pyruvate Imaging for Brain Cancer?

Research shows that hyperpolarized [1-13C]pyruvate can help detect treatment responses in brain tumors by highlighting changes in tumor metabolism, which is not easily visible with other imaging methods. This technique has been used to track tumor metabolism in both brain and breast cancer, suggesting its potential usefulness in monitoring how well treatments are working. ^{1 2 3 4 5}

Is Hyperpolarized C 13 Pyruvate Imaging safe for humans?

Hyperpolarized C 13 Pyruvate Imaging has been used safely in studies with healthy human volunteers and brain tumor patients, showing no reported safety issues during the imaging process. ^{1 6 7 8 9}

How does hyperpolarized C 13 pyruvate imaging differ from other brain cancer treatments?

Hyperpolarized C 13 pyruvate imaging is unique because it uses a special form of MRI to track the metabolism of pyruvate in real-time, providing detailed insights into tumor metabolism that other imaging methods can't offer due to high background signals in the brain. This technique allows for non-invasive monitoring of how brain tumors respond to treatments, which is not possible with standard imaging techniques. ^{1 4 9 10 11}

Research Team

Dawid Schellingerhout

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults over 18 with suspected or confirmed primary brain tumors who are candidates for tumor removal surgery. They must be able to undergo MRI scans and have a kidney function test (GFR) above 60. People with pacemakers, metal in their body, previous brain tumor treatments, or certain heart conditions cannot join.

Inclusion Criteria

Healthy volunteers should not have any issues with getting an MRI scan, but otherwise won't have any other requirements to participate.

You are going to have surgery to remove a suspected or confirmed primary brain tumor.

Written informed consent will be obtained from each participant including healthy volunteers

Exclusion Criteria

Healthy volunteers will be screened using the same process but will otherwise not be subject to other selection criteria

You have a pacemaker or other metal devices in your body that are not safe for MRI scans.

The patient's anatomy makes it unsafe to do a specific type of biopsy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive hyperpolarized carbon C 13 pyruvate intravenously and undergo an MRSI scan

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 day

1 visit (in-person)

Long-term follow-up

Participants' genomic, pathology, and imaging findings are assessed over time

Up to 1 year

Treatment Details

Interventions

• Hyperpolarized Carbon C 13 Pyruvate

Trial Overview Researchers are testing an imaging agent called hyperpolarized carbon C 13 pyruvate used before an advanced MRSI scan to see if it helps diagnose glioma more accurately in patients with brain tumors.

Participant Groups

Group I: Diagnostic (carbon C 13 pyruvate, MRSI) Experimental Treatment 2 Interventions

Patients receive hyperpolarized carbon C 13 pyruvate IV over 10-20 seconds and then undergo an MRSI scan.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

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]

In a study involving three patients with glioblastoma, 13C MR spectroscopic imaging using hyperpolarized pyruvate successfully detected increased lactate production in tumor regions prior to surgical resection, indicating altered metabolism in these aggressive tumors.

The imaging technique correlated well with histological findings, confirming the presence of WHO grade IV glioblastoma and suggesting that this method could help identify metabolic changes associated with tumor aggressiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative imaging of glioblastoma patients using hyperpolarized 13C pyruvate: Potential role in clinical decision making. Chen, J., Patel, TR., Pinho, MC., et al.[2022]

Hyperpolarized carbon-13 MRI (HP-13C MRI) showed consistent measurements of brain metabolism in both healthy volunteers and patients with diffuse infiltrating glioma, indicating its potential as a reliable non-invasive imaging technique for monitoring brain tumor treatment.

In patients treated with the anti-angiogenic agent bevacizumab, there were significant increases in metabolic rates (kPL and kPB) in normal-appearing white matter, while progressive disease was associated with elevated kPL in tumor lesions, suggesting that HP-13C MRI can detect metabolic changes related to tumor progression and treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of serial hyperpolarized 13C metabolic imaging in patients with glioma. Autry, AW., Gordon, JW., Chen, HY., et al.[2021]

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]

In a study involving 17 canine cancer patients, hyperpolarized 13C Magnetic Resonance Spectroscopy (MRS) showed significant correlations between pyruvate-to-lactate conversion and 18F-FDG uptake specifically in sarcoma patients, suggesting a link between lactate generation and cancer metabolism.

The research indicates that the relationship between lactate production and 18F-FDG uptake varies by cancer type, with sarcoma patients exhibiting higher lactate generation relative to 18F-FDG uptake compared to carcinoma patients, which could enhance the understanding of cancer metabolism and improve diagnostic imaging techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined hyperpolarized 13C-pyruvate MRS and 18F-FDG PET (hyperPET) estimates of glycolysis in canine cancer patients. Hansen, AE., Gutte, H., Holst, P., et al.[2019]

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 successfully hyperpolarized [1,2-13C]pyruvate with approximately 7% polarization, allowing for enhanced monitoring of its conversion to lactate in cancer cells using a new pulse sequence called MINERVA.

This method enables simultaneous observation of different chemical reactions and the detection of reaction intermediates, such as 2-hydroperoxy-2-hydroxypropanoate, in real time, which could improve our understanding of metabolic processes in cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-Time Pyruvate Chemical Conversion Monitoring Enabled by PHIP. Stevanato, G., Ding, Y., Mamone, S., et al.[2023]

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]

Hyperpolarized (HP) (13)C labeled compounds, particularly HP 1-(13)C pyruvate, are effective MR contrast agents that allow for real-time investigation of metabolic pathways in vivo, with the ability to track pyruvate metabolism for nearly 2 minutes post-injection.

The technique has expanded beyond tumor metabolism to non-invasively assess physiological parameters like pH, highlighting its growing potential in medical research, especially with the increasing availability of dynamic nuclear polarization (DNP) systems for generating hyperpolarized materials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperpolarized 13carbon MR. Rowland, IJ., Peterson, ET., Gordon, JW., et al.[2019]

A stable hyperpolarized solution of [1-(13)C]-ethyl pyruvate was successfully developed, allowing for its use in metabolic imaging studies.

In a study involving anesthetized rats, hyperpolarized [1-(13)C]-ethyl pyruvate was compared to [1-(13)C]-pyruvate, demonstrating its potential for effective uptake and metabolic imaging in the brain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolic imaging in the anesthetized rat brain using hyperpolarized [1-13C] pyruvate and [1-13C] ethyl pyruvate. Hurd, RE., Yen, YF., Mayer, D., et al.[2021]

Using multi-resolution hyperpolarized 13C pyruvate MRI in 6 subjects improved the measurement of kinetic conversion rates in the human brain, particularly by enhancing spatial resolution and reducing partial volume effects.

Higher resolution images (7.5 × 7.5 mm2) led to more accurate calculations of pyruvate-to-lactate conversion rates, especially in areas near blood vessels, indicating that finer resolution can significantly enhance metabolic data quality in brain imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Kinetic analysis of multi-resolution hyperpolarized 13 C human brain MRI to study cerebral metabolism. Hu, JY., Kim, Y., Autry, AW., et al.[2023]

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. England pubmed.ncbi.nlm.nih.gov

Preoperative imaging of glioblastoma patients using hyperpolarized 13C pyruvate: Potential role in clinical decision making. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Characterization of serial hyperpolarized 13C metabolic imaging in patients with glioma. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

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

5. Ireland pubmed.ncbi.nlm.nih.gov

Combined hyperpolarized 13C-pyruvate MRS and 18F-FDG PET (hyperPET) estimates of glycolysis in canine cancer patients. [2019]

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

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

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

Real-Time Pyruvate Chemical Conversion Monitoring Enabled by PHIP. [2023]

8. 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]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Hyperpolarized 13carbon MR. [2019]

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

Metabolic imaging in the anesthetized rat brain using hyperpolarized [1-13C] pyruvate and [1-13C] ethyl pyruvate. [2021]

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

Kinetic analysis of multi-resolution hyperpolarized 13 C human brain MRI to study cerebral metabolism. [2023]