Metabolic Imaging for Detecting Heart Damage After Radiation in Breast Cancer Patients

Overseen By Devin Holland, MS

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Texas Southwestern Medical Center

Must not be taking: Cardiotoxic agents

Disqualifiers: Prior heart radiation, Connective tissue disorders, eGFR <30, others

Stay on Your Current Meds You can continue your current medications while participating

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

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to detect early signs of heart damage in individuals receiving radiation therapy for certain breast or chest tumors. It employs a special imaging technique using [1-13C]pyruvate (also known as Hyperpolarized 13C-Pyruvate) and MRI to identify changes in mitochondrial function after radiation. This trial may suit those with a left-sided breast or chest tumor who are scheduled for radiation treatment. Those without prior heart radiation or heart-harming medications should consider participating. As an Early Phase 1 trial, this research seeks to understand how the treatment works in people, offering a unique opportunity to contribute to groundbreaking medical insights.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications. However, you cannot take any known cardiotoxic agents for 6 months before and during the study.

What prior data suggests that this method is safe for detecting heart damage?

Research has shown that using [1-13C]pyruvate with MRI scans holds promise in various medical areas. One study found that hyperpolarized [1-13C]pyruvate is safe at certain levels, allowing its use without major safety concerns. Other studies, such as those for cancer diagnosis, have also used this compound without significant safety issues. Evidence suggests it is generally well-tolerated in people, though further research is needed to confirm this in different contexts. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using [1-13C]pyruvate with MRI imaging because it provides a novel way to detect heart damage early in breast cancer patients undergoing radiation therapy. Unlike traditional methods that might rely on symptoms or standard imaging techniques, this approach uses a special compound, [1-13C]pyruvate, which can offer real-time insights into the heart's metabolic changes. This could potentially allow for earlier intervention, reducing the risk of severe cardiotoxicity and improving patient outcomes. By focusing on the heart's metabolism, this method provides a unique perspective that current imaging techniques may miss.

What evidence suggests that this imaging method is effective for detecting heart damage in breast cancer patients?

Research has shown that using a special form of pyruvate, called [1-13C]pyruvate, with MRI scans can effectively detect changes in heart metabolism. This trial will use [1-13C]pyruvate MRI to diagnose cardiotoxicity in breast cancer patients undergoing radiation therapy. Studies have found that this method can reveal metabolic changes in heart failure, potentially identifying early signs of heart damage. In previous research, [1-13C]pyruvate MRI successfully mapped metabolic changes in various cancers, such as breast cancer. This imaging technique allows doctors to assess heart function at a cellular level, especially after radiation treatments. Observing these changes may make it easier to detect heart damage before it becomes serious. ^{2 5 6 7 8}

Who Is on the Research Team?

Prasanna Alluri, MD, PhD

Principal Investigator

UTSW Radiation Oncology

Are You a Good Fit for This Trial?

This trial is for individuals with left-sided breast or thoracic tumors, stages I-IV, who are expected to live at least 6 months and can undergo standard radiation therapy. They must be able to perform daily activities (ECOG status 0-1), use contraception if of childbearing potential, and provide informed consent. Excluded are those with life expectancy under 6 months, prior heart radiation, taking cardiotoxic drugs within the last 6 months, severe illnesses or conditions that affect MRI safety.

Inclusion Criteria

I am fully active or can carry out light work.

I agree to use effective birth control or abstain from sex during and for 90 days after the study.

Ability to understand and the willingness to sign a written informed consent

Exclusion Criteria

I have been diagnosed with a connective tissue disorder like lupus, scleroderma, or dermatomyositis.

I do not have any severe illnesses or social situations that would stop me from following the study's requirements.

You have something in your body that can't be in the same room as a strong magnet, or you're very afraid of being in small, enclosed spaces.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Imaging

Participants undergo baseline magnetic resonance spectroscopic imaging with [1-13C]pyruvate injection and a proton MRI/spectroscopy scan prior to receipt of adjuvant radiation therapy

1 week

1 visit (in-person)

Radiation Treatment

Participants receive standard-of-care breast or chest wall radiation therapy

6-8 weeks

Post-treatment Imaging

Post-treatment imaging is performed to detect early changes in mitochondrial metabolism as a marker for subclinical radiation-induced cardiotoxicity

Within 3 months of completion of radiation treatments

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• [1-13C]pyruvate along with MRI imaging

Trial Overview [1-13C]pyruvate used in conjunction with MRI imaging aims to detect early mitochondrial changes in the heart as a marker for subclinical damage from radiation therapy in patients receiving standard care for breast or thoracic cancer. The study focuses on identifying cardiac injury before symptoms appear by monitoring metabolic shifts caused by treatment.

How Is the Trial Designed?

Group I: Single Arm:Diagnosing Cardiotoxicity when on Radiation therapy Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Published Research Related to This Trial

X-ray irradiation significantly alters pyruvate metabolism in tumors, as shown by changes in the lactate to pyruvate ratio (Lac/Pyr) detected using hyperpolarized (13)C-MRI in squamous cell carcinoma (SCCVII) and colon cancer (HT-29) models.

Irradiation reduced lactate dehydrogenase (LDH) activity in tumors, which contributed to the observed decrease in Lac/Pyr, indicating that monitoring these metabolic changes could be a valuable method for assessing the early response to radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

13C-MR Spectroscopic Imaging with Hyperpolarized [1-13C]pyruvate Detects Early Response to Radiotherapy in SCC Tumors and HT-29 Tumors. Saito, K., Matsumoto, S., Takakusagi, Y., et al.[2021]

Hyperpolarized ¹³C metabolic imaging using [1-¹³C]pyruvate can effectively detect early responses to radiation therapy in breast cancer tumors, showing significant decreases in lactate levels 96 hours post-treatment.

The study found that these metabolic changes correlated with increased cellular apoptosis and senescence in tumors, suggesting that this imaging technique could help tailor more effective treatment plans for patients undergoing radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Probing early tumor response to radiation therapy using hyperpolarized [1-¹³C]pyruvate in MDA-MB-231 xenografts. Chen, AP., Chu, W., Gu, YP., et al.[2021]

The study demonstrates the use of ParaHydrogen Induced Polarization (PHIP) with Side Arm Hydrogenation (SAH) to create hyperpolarized [1-13C]pyruvate for real-time metabolic imaging, which is a cost-effective and portable alternative to traditional methods.

In a mouse model of dilated cardiomyopathy, this imaging technique was able to detect metabolic dysfunction in cardiac muscle earlier than conventional echocardiographic methods, highlighting its potential as a sensitive marker for early organ damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The 13C hyperpolarized pyruvate generated by ParaHydrogen detects the response of the heart to altered metabolism in real time. Cavallari, E., Carrera, C., Sorge, M., et al.[2019]

A new imaging technique using co-polarized [1-13 C]pyruvate and 13 C-urea allows for simultaneous assessment of metabolism and blood flow (perfusion) in the hearts of healthy rats, demonstrating its feasibility in a study with 12 subjects.

The method successfully detected changes in heart metabolism through pyruvate conversion to bicarbonate and measured perfusion through variations in myocardial signals, paving the way for future research on cardiac metabolism and perfusion mismatches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simultaneous assessment of cardiac metabolism and perfusion using copolarized [1-13 C]pyruvate and 13 C-urea. Lau, AZ., Miller, JJ., Robson, MD., et al.[2022]

Hyperpolarized 13C MRI can effectively differentiate between radiation-induced necrosis and brain tumors based on metabolic differences, as shown in a study involving 20 mice with distinct models for radiation necrosis and tumors.

The study found that radiation necrosis had significantly lower levels of lactate and a lower lactate-to-pyruvate ratio compared to glioma and metastatic tumors, indicating that this imaging technique could enhance diagnostic accuracy in neuro-oncology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differentiating Radiation Necrosis from Brain Tumor Using Hyperpolarized Carbon-13 MR Metabolic Imaging. Park, I., Kim, S., Pucciarelli, D., et al.[2022]

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]

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 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]

In a study involving 5 pigs with dilated cardiomyopathy (DCM), hyperpolarized (13)C magnetic resonance imaging revealed that pyruvate oxidation was maintained early in the disease but significantly decreased as DCM progressed, indicating a decline in the heart's metabolic capacity.

The research demonstrated that early cardiac energetics changes, such as decreased phosphocreatine/ATP ratios and reduced glutamate production, occurred before the clinical features of DCM appeared, highlighting the potential of hyperpolarized (13)C MR to track metabolic alterations in heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperpolarized (13)C magnetic resonance reveals early- and late-onset changes to in vivo pyruvate metabolism in the failing heart. Schroeder, MA., Lau, AZ., Chen, AP., et al.[2022]

A novel hyperpolarization technique using dynamic nuclear polarization has significantly improved the ability to study real-time myocardial metabolism in both healthy and diseased hearts, overcoming the limitations of traditional magnetic resonance spectroscopy.

Research using hyperpolarized 13C labeled pyruvate has revealed important changes in heart metabolism related to conditions like diabetes and heart failure, suggesting potential clinical applications for diagnosing and treating cardiac diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical implications of cardiac hyperpolarized magnetic resonance imaging. Rider, OJ., Tyler, DJ.[2022]

Citations

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Comparison of 13C MRI of hyperpolarized [1‐13C]pyruvate ... Comparison of 13C MRI of hyperpolarized [1‐13C]pyruvate and lactate with the corresponding mass spectrometry images in a murine lymphoma model.

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

Hyperpolarized Pyruvate (13C) Injection ... Imaging of patients with prostate cancer using hyperpolarized [1-13C]pyruvate ... 13C MRI: a new horizon for noninvasive diagnosis of aggressive breast cancer ...

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Hyperpolarised 13C-MRI using 13C-pyruvate in breast ... This review summarises the current literature on preclinical and clinical research on hyperpolarised 13 C-MRI with [1- 13 C]-pyruvate in breast cancer imaging.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04044872

Study Details | NCT04044872 | Hyperpolarized Carbon 13- ... A first-in-human clinical study to evaluate the effect of cardiotoxic chemotherapy on [1-13C]Pyruvate metabolism is currently ongoing at UT Southwestern ( ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S1097664724011220

13 C]pyruvate cardiovascular magnetic resonance imaging ... This study highlighted the ability of HP [1- 13 C]pyruvate CMR to detect changes in metabolism in HF. HP [1- 13 C]pyruvate CMR has the potential for metabolic ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10224418/

Enhancing Cancer Diagnosis with Real-Time Feedback This review article discusses the potential of hyperpolarized (HP) 13 C magnetic resonance spectroscopic imaging (MRSI) as a noninvasive technique for ...

7. nature.com nature.com/articles/s41598-025-03454-1

Hyperpolarized [1- 13 C]pyruvate NMR spectroscopy ... These findings suggest that HP [1- 13 C]pyruvate NMR spectroscopy may serve as a metabolic biomarker for early-phase tumorigenesis in vivo.

8. pubs.rsna.org pubs.rsna.org/doi/full/10.1148/rycan.230005

Hyperpolarized Carbon 13 MRI: Clinical Applications and ... Hyperpolarized carbon 13 MRI ( 13 C MRI) is a novel imaging approach that can noninvasively probe tissue metabolism in both normal and pathologic tissues.