HP Pyruvate MRI for Cancer Detection

(HC-MRI Trial)

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Maryland, Baltimore

Disqualifiers: No tumor diagnosis

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: Unknown

Duration: 18-36 months

25 Participants Needed

Trial Summary

What is the purpose of this trial?

Many human diseases are characterized by their ability to alter existing metabolic pathways and interrupt cellular processes. Cancer exploits the Warburg effect and utilizes greater glucose than normal cells and within this process uses anaerobic respiration, leading to increased conversion of pyruvate to lactate. This can be exploited by hyperpolarized imaging. Hyperpolarized 13C MRI imaging is an approach that utilizes a stable isotope of Carbon (13C) linked to pyruvate. MRI spectroscopy is used in conjunction with hyperpolarized 13C pyruvate in order to temporally detect pyruvate and its conversion to lactate in-vivo, in order to visualize downstream metabolic (glycolytic) activity secondary to the Warburg effect, which should be useful in detecting and characterizing tumors of various types. Hyperpolarized 13C pyruvate MR imaging has not been tested in most cancers. In this preliminary survey, we will test the hypothesis that hyperpolarized 13C pyruvate MR imaging can be used to image various cancers.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the treatment Hyperpolarized 13C-Pyruvate MRI for cancer detection?

Research shows that Hyperpolarized 13C-Pyruvate MRI can provide detailed images of cancer metabolism, helping to detect tumors and monitor treatment response. Studies have demonstrated its potential in various cancers, including breast and prostate cancer, by tracking how cancer cells process energy differently from normal cells. ^{1 2 3 4 5}

Is HP Pyruvate MRI safe for humans?

Research indicates that HP Pyruvate MRI, including its various forms like Hyperpolarized 13C-Pyruvate, has been used in human studies and is considered non-toxic and safe for injection. The solution used in studies is sterile, pH neutral, and has been tested for safety in metabolic imaging. ^{1 3 6 7 8}

What makes HP 13C Pyruvate MRI unique for cancer detection?

HP 13C Pyruvate MRI is unique because it uses hyperpolarized carbon-13 labeled pyruvate to enhance MRI signals, allowing real-time tracking of tumor metabolism and early detection of treatment response. This method provides a non-invasive way to visualize metabolic changes in cancer cells, which is not possible with standard imaging techniques. ^{1 7 9 10 11}

Eligibility Criteria

This trial is for patients who already have scheduled MR imaging appointments, can safely undergo an MRI scan, and have a clinical diagnosis of a tumor. It's not open to individuals without a tumor diagnosis.

Inclusion Criteria

I have been diagnosed with a tumor.

Patients with pre-existing MR imaging appointments

Must be able to undergo MR

Exclusion Criteria

I have not been diagnosed with a tumor.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive an injection of 250 mM of hyperpolarized 13-C pyruvate intravenously and undergo HP-MR imaging

18-36 months

Follow-up

Participants are monitored for imaging quality and metabolic changes after treatment

12-42 months

Treatment Details

Interventions

• Hyperpolarized 13C-Pyruvate

Trial Overview The study tests if hyperpolarized 13C pyruvate MRI can image various cancers by tracking the conversion of pyruvate to lactate—a process that's more active in cancer cells due to altered metabolism known as the Warburg effect.

Participant Groups

Group I: Experimental Experimental Treatment 1 Intervention

Participants will receive an injection of 250 mM of hyperpolarized 13-C pyruvate intravenously after standard of care imaging sequences are performed. Then participants will undergo HP-MR imaging.

Hyperpolarized 13C-Pyruvate is already approved in United States, European Union for the following indications:

Approved in United States as Hyperpolarized 13C Pyruvate MRI for:

• Prostate cancer
• Research use in various cancers

Approved in European Union as Hyperpolarized 13C Pyruvate MRI for:

• Research use in various cancers

Who Is Running the Clinical Trial?

University of Maryland, Baltimore

Lead Sponsor

Trials

729

Recruited

540,000+

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]

Hyperpolarized 13C MRI has shown promise in providing unique metabolic insights into cancer, with a dose-ranging study confirming its safety and feasibility in patients with prostate cancer.

Ongoing research is exploring the use of hyperpolarized agents in various cancer types, and advancements in technology and collaboration among academia, industry, and government are essential for translating this imaging technique into clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperpolarized 13C MRI: Path to Clinical Translation in Oncology. Kurhanewicz, J., Vigneron, DB., Ardenkjaer-Larsen, JH., et al.[2023]

Hyperpolarized magnetic resonance imaging (HP-MRI) using (13)C-pyruvate is a promising tool for quantitatively assessing how solid tumors respond to radiotherapy and for monitoring potential toxicity in normal tissues.

This imaging technique can effectively predict responses related to metabolic changes in tumors, although there are still challenges to overcome for its successful use in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolic Imaging as a Biomarker of Early Radiation Response in Tumors. Lai, SY., Fuller, CD., Bhattacharya, PK., et al.[2018]

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 (HP) 13C metabolic imaging is emerging as a promising clinical diagnostic tool for cancer, leveraging the unique metabolic changes in cancer cells to detect and monitor tumors.

The effectiveness of HP 13C MRI relies on advancements in MRI technology and pulse sequence design to optimize the detection of HP signals, particularly focusing on the use of HP pyruvate to identify lactate pools linked to cancer metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cancer in the crosshairs: targeting cancer metabolism with hyperpolarized carbon-13 MRI technology. von Morze, C., Merritt, ME.[2023]

Hyperpolarized 13C MRI, particularly using [1-13C]pyruvate, is a promising technique for measuring localized metabolism in various diseases, including cancers and organ disorders, and has seen significant advancements in human studies over the past decade.

The paper outlines essential practices for conducting successful HP 13C MRI studies, covering preparation, MRI setup, data acquisition, and analysis, while also highlighting current evidence gaps and limitations in the field.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current Methods for Hyperpolarized [1-13C]pyruvate MRI Human Studies. Larson, PE., Bernard, JM., Bankson, JA., et al.[2023]

The study introduces a new method called Signal Amplification By Reversible Exchange (SABRE) that allows for the rapid production of hyperpolarized pyruvate for MRI, achieving results in just 6 minutes, making it a faster and more accessible option for metabolic imaging.

The produced hyperpolarized pyruvate solution is sterile, non-toxic, and pH neutral, indicating its safety for use in living organisms, which enhances its potential for diagnosing and monitoring cancer and other diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In Vivo Metabolic Imaging of [1-13 C]Pyruvate-d3 Hyperpolarized By Reversible Exchange With Parahydrogen. de Maissin, H., Groß, PR., Mohiuddin, O., et al.[2023]

Nuclear Magnetic Resonance (NMR) can non-invasively detect and quantify metabolites in cells and tissues, revealing metabolic changes without destroying samples, although its sensitivity is traditionally low.

Recent advancements in hyperpolarization techniques, particularly ParaHydrogen Induced Polarization (PHIP), allow for a cost-effective and rapid increase in the detection sensitivity of metabolites like hyperpolarized pyruvate, which has been effectively used to study metabolic changes in prostate cancer cell lines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In-vitro NMR Studies of Prostate Tumor Cell Metabolism by Means of Hyperpolarized [1-13C]Pyruvate Obtained Using the PHIP-SAH Method. Cavallari, E., Carrera, C., Di Matteo, G., et al.[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]

A new method using para-hydrogen allows for the rapid hyperpolarization of 13C-labeled substrates, achieving a polarization level of 24% for a precursor and 8% for free [1-13C]pyruvate, which significantly enhances magnetic resonance signals.

This technique enables real-time monitoring of metabolic processes, such as the conversion of pyruvate to lactate in cancer cells, highlighting its potential for advancing biomedical research and applications in magnetic resonance imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Field-Independent Method for the Rapid Generation of Hyperpolarized [1-13 C]Pyruvate in Clean Water Solutions for Biomedical Applications. Mamone, S., Jagtap, AP., Korchak, S., et al.[2022]

The study introduces a new method that allows for the detection of hyperpolarized [1-13C]pyruvate using standard proton-only MRI scanners, which could make this advanced imaging technique more accessible for clinical use.

By employing innovative pulse sequences to transfer hyperpolarization from carbon to protons, the method overcomes limitations related to specialized equipment, potentially enhancing the scalability of hyperpolarized MRI for diagnosing metabolic diseases like cancer and cardiovascular conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delivering Robust Proton-Only Sensing of Hyperpolarized [1,2-13C2]-Pyruvate Using Broad-Spectral-Range Nuclear Magnetic Resonance Pulse Sequences. Mandzhieva, I., Adelabu, I., Nantogma, S., et al.[2023]

References

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

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

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

Hyperpolarized 13C MRI: Path to Clinical Translation in Oncology. [2023]

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

Metabolic Imaging as a Biomarker of Early Radiation Response in Tumors. [2018]

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

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

5. England pubmed.ncbi.nlm.nih.gov

Cancer in the crosshairs: targeting cancer metabolism with hyperpolarized carbon-13 MRI technology. [2023]

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

Current Methods for Hyperpolarized [1-13C]pyruvate MRI Human Studies. [2023]

7. Germany pubmed.ncbi.nlm.nih.gov

In Vivo Metabolic Imaging of [1-13 C]Pyruvate-d3 Hyperpolarized By Reversible Exchange With Parahydrogen. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

In-vitro NMR Studies of Prostate Tumor Cell Metabolism by Means of Hyperpolarized [1-13C]Pyruvate Obtained Using the PHIP-SAH Method. [2020]

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

Hyperpolarized 13carbon MR. [2019]

10. Germany pubmed.ncbi.nlm.nih.gov

A Field-Independent Method for the Rapid Generation of Hyperpolarized [1-13 C]Pyruvate in Clean Water Solutions for Biomedical Applications. [2022]

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

Delivering Robust Proton-Only Sensing of Hyperpolarized [1,2-13C2]-Pyruvate Using Broad-Spectral-Range Nuclear Magnetic Resonance Pulse Sequences. [2023]