Hyperpolarized [13C] Pyruvate Imaging for Healthy Subjects

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Diabetes, Renal disorders, Claustrophobia, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how a special imaging agent, [13C]pyruvate (a hyperpolarized imaging agent), can enhance MRI scans. Researchers aim to observe how this agent spreads and changes in the organs and tissues of healthy individuals. For some participants, the study will test different injection speeds to determine the most effective method for brain imaging. Healthy individuals with no history of diabetes or kidney issues, and who can undergo an MRI scan, may be suitable for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to experience this innovative imaging approach.

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 study team or your doctor.

What prior data suggests that this imaging agent is safe for use in MRI scans?

Research has shown that hyperpolarized [13C] pyruvate is generally safe for humans. In earlier studies, participants handled the procedure well, with no negative effects reported up to a month afterward, suggesting the treatment is well-tolerated. Another study confirmed the safety of [13C] pyruvate, particularly for imaging. These findings indicate that this imaging agent is safe for human use. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because hyperpolarized [13C] pyruvate imaging offers a novel way to explore cellular metabolism in real-time. Unlike traditional imaging methods, this technique provides enhanced visualization of metabolic processes, giving detailed insights into how tissues use energy. The trial aims to optimize this imaging protocol, which could revolutionize the way we understand and diagnose various health conditions by providing more precise and immediate metabolic information.

What evidence suggests that hyperpolarized [13C] pyruvate is effective for MRI imaging?

Research shows that hyperpolarized [13C] pyruvate can clarify MRI scans by providing a better view of the body's energy use. Studies have found it useful for tracking changes in energy processing, particularly in understanding diseases like cancer. For instance, it has detected early responses to cancer treatments. This imaging agent reveals how different tissues use energy, offering detailed insights into organ function. Although more research is needed, these early findings suggest that [13C] pyruvate could enhance MRI's effectiveness in studying health and disease. Participants in this trial will join either the protocol optimization cohort or the tissue reference cohort, both using hyperpolarized [13C] pyruvate to improve MRI imaging. ^{6 7 8 9 10}

Who Is on the Research Team?

Vesselin Miloushev, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for healthy individuals aged 18-80. Women of childbearing age must have a negative pregnancy test before joining. The study excludes those with acute major illnesses, an inability to tolerate MRI scans (like claustrophobia), MR unsafe devices in their body, or history of metabolic and renal disorders.

Inclusion Criteria

Fifty healthy volunteers will be included

Exclusion Criteria

Breast-feeding

I do not have any severe illnesses like heart problems or widespread cancer.

I have diabetes or kidney problems.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive [13C]pyruvate injections followed by dynamic and 3D volumetric imaging using MRI

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Hyperpolarized [13C] Pyruvate

Trial Overview [13C]Pyruvate is being tested as an imaging agent for MRI scans in this study. Researchers want to understand how it's distributed in the body and metabolized by healthy organs and tissues during the scanning process.

How Is the Trial Designed?

Group I: Tissue reference cohort Experimental Treatment 1 Intervention

The optimal setup will then be used for HP MRI of the second cohort.

Group II: Protocol optimization cohort Experimental Treatment 1 Intervention

Following the \[13C\]pyruvate injection, dynamic imaging and 3D volumetric imaging of volunteers in the first cohort (HP MRI protocol optimization, Aim 1) will be performed on the 3-T MRI scanner, using different \[13C\] RF excitation/detection coils.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Sunnybrook Health Sciences Centre

Collaborator

Trials

693

Recruited

1,569,000+

Published Research Related to This Trial

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]

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]

The study successfully developed methods to prepare hyperpolarized [2-13C]pyruvate for the first human NMR studies, demonstrating its feasibility for investigating brain energy metabolism in four healthy volunteers.

Results showed that the conversion of hyperpolarized [2-13C]pyruvate to [2-13C]lactate and [5-13C]glutamate can be measured, with conversion rates comparable to previous studies using [1-13C]pyruvate, indicating the potential for this technique in metabolic research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First hyperpolarized [2-13C]pyruvate MR studies of human brain metabolism. Chung, BT., Chen, HY., Gordon, J., et al.[2022]

This study demonstrates the successful use of hyperpolarized 13C spectroscopy to detect metabolic products in the rat brain, specifically identifying [1-(13)C]lactate and [13C]bicarbonate after injecting [1-(13)C]pyruvate.

The research highlights the potential of using hyperpolarized [2-(13)C]pyruvate to detect [2-(13)C]lactate, although it did not reveal other metabolites, indicating that different pyruvate isotopes can yield varying insights into metabolic processes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo 13C spectroscopy in the rat brain using hyperpolarized [1-(13)C]pyruvate and [2-(13)C]pyruvate. Marjańska, M., Iltis, I., Shestov, AA., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6490043/

Hyperpolarized 13C MRI: State of the Art and Future Directions Notably, there was negligible change in the size of tumor on T2-weighted MR images and only a modest change on ADC images, supporting the utility of HP [1-13C] ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2319417024001057

Advancements, challenges, and future prospects in clinical ... HP 13C MRI, on the other hand, can provide detailed information on specific metabolic pathways, such as Krebs cycle activity in tumors, offering deeper insights ...

3. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/mrm.29875

Current methods for hyperpolarized [1‐13C]pyruvate MRI ... MRI with hyperpolarized (HP) 13C agents, also known as HP 13C MRI, can measure processes such as localized metabolism that is altered in ...

4. pubs.rsna.org pubs.rsna.org/doi/full/10.1148/rycan.2020200017

Hyperpolarized 13 C MRI of Tumor Metabolism ... Hyperpolarized 13 C MRI enabled successful identification of breast cancer response after one cycle of neoadjuvant chemotherapy and may improve response ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05599048

Hyperpolarized 13C MRI as a Biomarker in Advanced ... This is a single center prospective imaging study investigating the utility of hyperpolarized 13C-pyruvate +/-13C,15N-Urea/ metabolic MR imaging.

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

Hyperpolarized Pyruvate (13C) Injection Safety studies of the cardiovascular effects of the hyperosmotic pyruvate ... safety pharmacology data support adequate safety of Hyperpolarized Pyruvate (13C) ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38205934/

13 C]pyruvate in D 2 O for hyperpolarized MRI of the brain: A ... Conclusions: HP [1-13C]pyruvate in D2O is safe for human imaging and provides an increase in T1 and SNR that may improve image quality. Keywords ...

8. nature.com nature.com/articles/s41391-019-0180-z

Hyperpolarized 13 C-pyruvate MRI detects real-time ... HP 13 C-pyruvate MRI can detect real-time glycolytic metabolism within prostate cancer metastases, and can measure changes in quantitative k PL values ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5102279/

Hyperpolarized 13C Metabolic MRI of the Human Heart All subjects tolerated the procedure well with no adverse effects reported ≤1 month post procedure. The [1-13C]pyruvate signal appeared within the chambers but ...

10. sciencedirect.com sciencedirect.com/science/article/pii/S1053811923005013

Hyperpolarized [2–13C]pyruvate MR molecular imaging ... Hyperpolarized (HP) 13 C Magnetic Resonance Imaging (MRI) was applied for the first time to image and quantify the uptake and metabolism of [2– 13 C]pyruvate ...