Hyperpolarized Pyruvate Imaging for Cancer

Recruiting at 1 trial location

Overseen By Hedvig Hricak, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Breastfeeding, Claustrophobia, Hepatic, Renal, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

109 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of the study is to test a new approach to see if the test results can be reproduced each time the Magnetic resonance imaging (MRI) is done for an individual patient. The study will explore the use of an imaging agent called hyperpolarized \[1-13C\] pyruvate (HP) with MRI scans. (MRI) is a technique that takes pictures of the body's organs using a magnetic field and radiofrequency waves that cannot be felt. In order to accomplish the goal of the study the patient will have two hyperpolarized MRI scans to assess if scans can be reproduced. The hyperpolarized MRI scans will be compared with the pathological results of the surgery to see if the hyperpolarized MRI provides additional information regarding disease metabolism.

Will I have to stop taking my current medications?

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 Pyruvate Imaging for Cancer?

Research shows that hyperpolarized pyruvate imaging can help track cancer metabolism by highlighting how cancer cells process energy differently, which can be useful for early detection and monitoring treatment response. Studies in breast cancer have demonstrated that this imaging technique can identify changes in tumor metabolism before structural changes occur, potentially allowing for earlier intervention. ^{1 2 3 4 5}

Is hyperpolarized pyruvate imaging safe for humans?

The research on hyperpolarized pyruvate imaging, particularly in cancer studies, suggests it is generally safe for use in humans. Clinical feasibility has been demonstrated in breast cancer patients, and the technique is being explored for its potential in metabolic imaging without reported safety concerns. ^{1 3 6 7 8}

How does hyperpolarized pyruvate imaging differ from other cancer treatments?

Hyperpolarized pyruvate imaging is unique because it uses a special form of MRI to track the metabolism of cancer cells in real-time, providing detailed insights into tumor activity. This method enhances the detection sensitivity by thousands of times, allowing for early identification of treatment responses, unlike traditional imaging techniques. ^{1 7 9 10 11}

Research Team

Kayvan Keshari, PhD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for patients with certain cancers (sarcoma, prostate, breast, brain, metastatic or pancreatic) who can undergo MRI scans. They must not be pregnant or breastfeeding and should have a tumor that's measurable. People with severe liver or kidney issues, major illnesses like unstable heart conditions, or those who cannot tolerate an MRI due to devices like pacemakers are excluded.

Inclusion Criteria

My cancer diagnosis was confirmed by a pathology department, or I have suspected brain cancer based on MRI.

My cancer can be measured or seen on scans, with a tumor larger than 1cm.

I am not pregnant, confirmed by a recent test.

Exclusion Criteria

Standard MRI exclusion criteria will also be applied, including pacemakers and metal clips located in the patient

I cannot or will not have an IV line placed for a pyruvate injection.

I do not have any severe illnesses like heart problems.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging

Participants undergo two hyperpolarized MRI scans to assess reproducibility

1-2 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging

4 weeks

Treatment Details

Interventions

• Hyperpolarized Pyruvate

Trial Overview The study tests the reliability of hyperpolarized [1-13C] pyruvate (HP) in MRI scans for cancer patients by conducting two HP-MRI scans to see if they produce consistent results each time. It also compares these images with surgical pathology to check if it offers extra details on disease metabolism.

Participant Groups

Group I: Hyperpolarized Pyruvate MRI Reproducibility Experimental Treatment 1 Intervention

This is a reproducibility study of hyperpolarized \[1-13C\] pyruvate MRI in patients with solid tumors. A total of 100 patients will be enrolled, 50 of whom will be imaged using 1D MR spectroscopy and the other 50 with 3D imaging sequence.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Findings from Research

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]

Hyperpolarised carbon-13 (13C)-MRI is a novel imaging technique that allows for dynamic imaging of tumor metabolism, particularly the conversion of [1-13C]pyruvate to [1-13C]lactate, which is relevant in cancer due to the Warburg effect.

Clinical studies have shown that hyperpolarised 13C-MRI can effectively differentiate between higher grade breast tumors and predict treatment responses to neoadjuvant chemotherapy by measuring early changes in 13C-label exchange.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperpolarised 13C-MRI using 13C-pyruvate in breast cancer: A review. Arponen, O., Wodtke, P., Gallagher, FA., et al.[2023]

Hyperpolarized carbon 13 MRI (13C MRI) is a groundbreaking imaging technique that allows for real-time, noninvasive observation of tissue metabolism, particularly useful in cancer research.

This method has shown promise in clinical applications such as tumor grading, tailoring treatment based on metabolic profiles, and detecting early treatment responses by monitoring metabolic changes before structural alterations in tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperpolarized Carbon 13 MRI: Clinical Applications and Future Directions in Oncology. Deen, SS., Rooney, C., Shinozaki, A., et al.[2023]

Hyperpolarized 13C-labelled cell substrates, like hyperpolarized pyruvate, could revolutionize anatomic imaging in oncology by providing new metabolic metrics for assessing treatment responses.

This imaging technique offers a more personalized approach to evaluating patients at different stages of cancer treatment, potentially improving clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dynamic nuclear polarisation: The future of imaging in oncology? Serrao, EM., Brindle, KM.[2020]

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]

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]

The study introduces a new method, PHIP-SAH, for hyperpolarizing [1-13 C]pyruvate, which allows for real-time monitoring of metabolic processes in cancer research, particularly in glycolytic pathways.

Using this method, researchers successfully applied hyperpolarized [1-13 C]pyruvate to investigate glycolysis in two breast cancer cell lines, validating their findings with traditional biochemical assays, indicating its potential for broader cancer studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolic Studies of Tumor Cells Using [1-13 C] Pyruvate Hyperpolarized by Means of PHIP-Side Arm Hydrogenation. Cavallari, E., Carrera, C., Aime, S., et al.[2019]

Hyperpolarized carbon-13 (13C) MRI is a groundbreaking imaging technique that allows for real-time, noninvasive observation of metabolic processes in diseases like cancer and cardiovascular conditions, which were previously difficult to study.

The review highlights the promising clinical applications of HP [1-13C]pyruvate MRI, suggesting it could enhance our understanding of metabolism, improve disease diagnosis, and speed up treatment evaluations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperpolarized 13C MRI: State of the Art and Future Directions. Wang, ZJ., Ohliger, MA., Larson, PEZ., et al.[2020]

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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

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

2. Ireland pubmed.ncbi.nlm.nih.gov

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

3. Ireland pubmed.ncbi.nlm.nih.gov

Hyperpolarised 13C-MRI using 13C-pyruvate in breast cancer: A review. [2023]

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

Hyperpolarized Carbon 13 MRI: Clinical Applications and Future Directions in Oncology. [2023]

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

Dynamic nuclear polarisation: The future of imaging in oncology? [2020]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Hyperpolarized 13carbon MR. [2019]

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

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

8. Germany pubmed.ncbi.nlm.nih.gov

Metabolic Studies of Tumor Cells Using [1-13 C] Pyruvate Hyperpolarized by Means of PHIP-Side Arm Hydrogenation. [2019]

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

Hyperpolarized 13C MRI: State of the Art and Future Directions. [2020]

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

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

11. 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]