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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore a new method for diagnosing brain tumors, specifically gliomas, using an advanced imaging technique. The trial uses an imaging agent called hyperpolarized carbon C 13 pyruvate, administered before a special MRI scan to enhance the visibility and understanding of the brain tumor. Participants with a brain tumor who plan to undergo surgery for its removal are being sought. As a Phase 1 trial, the research focuses on understanding how this new imaging technique functions in people, offering participants the opportunity to be among the first to benefit from this innovative approach.

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 prior data suggests that this imaging agent is safe for diagnosing glioma?

Research shows that hyperpolarized carbon C 13 pyruvate is being tested as a safe diagnostic tool for brain tumors. Earlier studies used it to highlight metabolic changes in brain tumors, aiding doctors in clearer understanding and visualization.

Patients who received this treatment generally tolerated it well, with no serious side effects reported. This indicates that most people handle the treatment without major issues. As this trial is in its early stages, the primary goal is to ensure the treatment's safety for humans. So far, studies suggest that hyperpolarized carbon C 13 pyruvate is a promising and safe tool for improving brain tumor diagnosis. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about hyperpolarized carbon C 13 pyruvate imaging for brain cancer because it offers a new way to visualize cancer metabolism in real-time. Unlike standard imaging techniques that mainly show the tumor's size or shape, this method uses hyperpolarized carbon C 13 pyruvate as a contrast agent in an MRSI scan to highlight active cancer cells by tracking how they process nutrients. This allows for a more precise understanding of tumor activity and could lead to earlier and more tailored treatment decisions.

What evidence suggests that hyperpolarized carbon C 13 pyruvate is effective for diagnosing glioma?

Research has shown that hyperpolarized carbon C 13 pyruvate, which participants in this trial will receive, can enhance brain scans for detecting tumors such as glioma. This substance helps produce clear images of brain activity, highlighting active tumor areas. The scanning method is non-invasive, requiring no surgery, and aims to provide a more detailed view of tumor activity. Early results suggest it could serve as a useful marker for tracking brain cancer, aiding doctors in identifying and monitoring the disease more effectively. ^{4 6 7 8 9}

Who Is on the Research Team?

Dawid Schellingerhout

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 (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]

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]

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 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]

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6050093/

Metabolic Imaging of the Human Brain with Hyperpolarized ... Here we present the first dynamically acquired human brain HP 13C metabolic spectra and spatial metabolite maps in cases of both untreated and recurrent tumors.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03739411

Study Details | NCT03739411 | Hyperpolarized Imaging in ... This pilot trial studies the side effects of hyperpolarized carbon C 13 pyruvate magnetic resonance imaging (MRI) in diagnosing participants with glioma.

3. sciencedirect.com sciencedirect.com/science/article/pii/S2213158220301601

Characterization of serial hyperpolarized 13C metabolic ... Hyperpolarized carbon-13 (HP-13C) MRI is a non-invasive imaging technique for probing brain metabolism, which may improve clinical cancer surveillance.

4. aacrjournals.org aacrjournals.org/cancerres/article/78/14/3755/631786/Metabolic-Imaging-of-the-Human-Brain-with

Metabolic Imaging of the Human Brain with Hyperpolarized 13 ... Hyperpolarized pyruvate MRI enables metabolic imaging in the brain and can be a quantitative biomarker for active tumors.

5. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT03739411

Hyperpolarized Imaging in Diagnosing Participants With ... This pilot trial studies the side effects of hyperpolarized carbon C 13 pyruvate magnetic resonance imaging (MRI) in diagnosing participants with glioma.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10546364/

Hyperpolarized Carbon 13 MRI: Clinical Applications and ... Clinical hyperpolarized carbon 13 MRI has been shown to identify occult tumors, stratify lesions based on histologic grade, and detect early response to ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03067467

Metabolic Characteristics of Brain Tumors Using ... The aim of this pilot study is to test the hypothesis that patients with brain malignancy present altered [1-13C]lactate and 13C-bicarbonate production from ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6260457/

Hyperpolarized 13C MRI: Path to Clinical Translation in ... Metabolic imaging of the human brain with hyperpolarized (13)C pyruvate demonstrates (13)C lactate production in brain tumor patients. Cancer Res. 2018;78 ...

9. dctd.cancer.gov dctd.cancer.gov/drug-discovery-development/reagents-materials/imaging-ind-resources/documentation/13c-pyruvate-ib.pdf

Hyperpolarized Pyruvate (13C) Injection Hyperpolarized Carbon C 13 Pyruvate in. Diagnosing Glioma in Patients with Brain. Tumors. Recruiting. Primary Brain Neoplasm. M D Anderson Cancer. Center, ...