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

Recruiting in Palo Alto (17 mi)

Overseen by Prasanna Alluri, MD, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Recruiting

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

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial uses advanced imaging techniques to detect early heart damage in women with left-sided breast cancer receiving radiation therapy. By observing how the heart processes a special substance, doctors can identify early signs of damage before it becomes severe.

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 data supports the idea that Metabolic Imaging for Detecting Heart Damage After Radiation in Breast Cancer Patients is an effective treatment?

The available research shows that Metabolic Imaging using Hyperpolarized 13C-Pyruvate is effective in detecting heart damage by allowing real-time monitoring of metabolism. In a study with mice, it was able to detect heart muscle problems before they could be seen with other methods. This suggests it could be a useful tool for early detection of heart issues. Additionally, it has been shown to help differentiate between radiation damage and tumor recurrence in brain studies, indicating its potential for broader applications in detecting tissue changes. ^{1 2 3 4 5}

What safety data exists for using hyperpolarized [1-13C]pyruvate in imaging treatments?

The safety and feasibility of hyperpolarized [1-13C]pyruvate in imaging treatments have been demonstrated in clinical studies, particularly in breast cancer imaging. The technique allows for non-invasive, real-time detection of metabolic changes without ionizing radiation. While the technology is still developing, it has shown potential for early detection of treatment responses and metabolic phenotyping. However, specific safety data such as adverse effects or long-term outcomes are not detailed in the provided research abstracts. ^{2 4 6 7 8}

Is the treatment [1-13C]pyruvate with MRI imaging a promising way to detect heart damage after radiation in breast cancer patients?

Yes, [1-13C]pyruvate with MRI imaging is promising because it allows real-time monitoring of heart metabolism, can detect heart damage early, and provides detailed metabolic information that was previously hard to access. ^{4 5 8 9 10}

Research Team

Prasanna Alluri, MD, PhD

Principal Investigator

UTSW Radiation Oncology

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• [1-13C]pyruvate along with MRI imaging (Metabolic Imaging Agent)

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.

Participant Groups

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+

Daniel K. Podolsky

University of Texas Southwestern Medical Center

Chief Executive Officer since 2008

MD from Harvard Medical School

Robert L. Bass

University of Texas Southwestern Medical Center

Chief Medical Officer since 2019

MD from University of Texas Southwestern Medical School

Findings from Research

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]

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]

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]

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]

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]

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 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]

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 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]

References

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

Differentiating Radiation Necrosis from Brain Tumor Using Hyperpolarized Carbon-13 MR Metabolic Imaging. [2022]

2. United States 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. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Clinical implications of cardiac hyperpolarized magnetic resonance imaging. [2022]

4. Ireland pubmed.ncbi.nlm.nih.gov

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

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

The 13C hyperpolarized pyruvate generated by ParaHydrogen detects the response of the heart to altered metabolism in real time. [2019]

6. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

Probing early tumor response to radiation therapy using hyperpolarized [1-¹³C]pyruvate in MDA-MB-231 xenografts. [2021]

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

Hyperpolarized MRI - An Update and Future Perspectives. [2022]

9. England 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. [2022]

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

Simultaneous assessment of cardiac metabolism and perfusion using copolarized [1-13 C]pyruvate and 13 C-urea. [2022]