Hyperpolarized 13C Pyruvate MRI for Kidney Cancer

Overseen By Maya Aslam

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Zhen Wang, MD

Disqualifiers: Uncontrolled hypertension, Congestive heart failure, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 1 day

100 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you have poorly controlled high blood pressure, you may need to adjust your medication to qualify for the study.

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

Research shows that Hyperpolarized 13C Pyruvate MRI can help assess tumor aggressiveness in kidney cancer by measuring how tumors convert pyruvate to lactate, which is linked to tumor grade and survival. This imaging technique has been used successfully in other cancers, like prostate cancer, to evaluate metabolic changes, suggesting its potential usefulness in kidney cancer as well. ^{1 2 3 4 5}

Is Hyperpolarized 13C Pyruvate MRI safe for humans?

A study on patients with prostate cancer showed that using Hyperpolarized 13C Pyruvate MRI is safe and feasible, and ongoing studies are exploring its use in other cancers like brain, breast, and liver cancer. ^{2 5 6 7 8}

How is the treatment Hyperpolarized 13C Pyruvate MRI unique for kidney cancer?

Hyperpolarized 13C Pyruvate MRI is unique because it allows real-time imaging of kidney cancer metabolism, providing insights into metabolic changes that are not accessible with traditional imaging methods. This technique uses a special form of pyruvate to track how cancer cells process energy, offering a novel way to assess tumor activity and potentially guide treatment decisions. ^{2 3 5 9 10}

What is the purpose of this trial?

This feasibility study will evaluate how well hyperpolarized 13C pyruvate magnetic resonance imaging (MRI) scan works in predicting tumor aggressiveness in participants with renal tumors. Hyperpolarized 13C pyruvate is a non-radioactive substance with potential usage in the diagnostic imaging of tumors. Hyperpolarized 13C pyruvate MRI may help doctors determine non-invasively whether a kidney tumor is a benign tumor or cancer, and if cancer, how aggressive it is. This may help doctors and participants with renal tumors in the future to make better treatment decisions.

Research Team

Zhen Jane Wang, MD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

This trial is for adults with kidney tumors larger than 1 cm who can follow study procedures and give informed consent. They should be fit enough for potential kidney surgery or active monitoring, with a good performance status (able to carry out daily activities). People with metal implants affecting MRI quality, heart failure, uncontrolled high blood pressure, or those unable to undergo MRI are excluded.

Inclusion Criteria

Participant able and willing to comply with study procedures and provide signed and dated informed consent

My doctor is considering surgery, ablation, or monitoring for my kidney tumor.

My kidney tumor is at least 1 cm big.

Exclusion Criteria

My blood pressure is higher than 160/100 despite medication.

I have heart failure or my condition limits my physical activity.

Participants unwilling or unable to undergo magnetic resonance (MR) imaging, including patients with contra-indications to MR imaging such as cardiac pacemakers or non-compatible intracranial vascular clips

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive HP 13C pyruvate intravenously and undergo MRI scan 1-2 minutes post injection. An optional second scan may occur 15 to 30 minutes later or within 1-2 weeks.

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 minutes

Long-term monitoring

Participants' metabolic data and tumor growth are monitored for up to 12 months

12 months

Treatment Details

Interventions

• Hyperpolarized 13C Pyruvate

Trial Overview The study tests if a special type of MRI scan using hyperpolarized 13C pyruvate can predict how aggressive kidney tumors are without invasive procedures. This non-radioactive imaging technique could help doctors and patients choose the best treatment by distinguishing between benign and cancerous tumors.

Participant Groups

Group I: Diagnostic (HP 13C pyruvate with MRI) Experimental Treatment 2 Interventions

Participants receive HP 13C pyruvate IV and then undergo 13C MRI scan 1-2 minutes post HP 13C pyruvate injection. Participants may receive an optional second HP 13C pyruvate injection and undergo 13C pyruvate MRI scan 15 to 30 minutes following completion of the first scan or at a return visit 1-2 weeks from the first HP C13 MRI

Group II: Diagnostic (Combined (co-polarized) HP 13C pyruvate and 13C, 15N2 Urea with MRI) Experimental Treatment 3 Interventions

Participants receive HP 13C pyruvate and 13C 15N2 urea IV and then undergo an MRI scan 1-2 minutes post injection. Participants may receive an optional second HP 13C pyruvate with 13C 15N2 urea injection and undergo a second MRI scan 15 to 30 minutes following completion of the first scan or at a return visit 1-2 weeks from the first HP C13 MRI

Who Is Running the Clinical Trial?

Zhen Wang, MD

Lead Sponsor

Trials

2

Recruited

110+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

American Cancer Society, Inc.

Collaborator

Trials

237

Recruited

110,000+

Findings from Research

Metabolic imaging using carbon-13 MRI (HP-13C-MRI) can effectively differentiate aggressive clear cell renal cell carcinoma (ccRCC) from less aggressive tumors, showing a strong correlation between the imaging results and tumor grade.

The study found that higher levels of the pyruvate transporter MCT1, which were linked to tumor aggressiveness, also predicted overall and disease-free survival in patients, suggesting that HP-13C-MRI could be a valuable non-invasive tool for assessing renal cancer aggressiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperpolarized 13C-Pyruvate Metabolism as a Surrogate for Tumor Grade and Poor Outcome in Renal Cell Carcinoma-A Proof of Principle Study. Ursprung, S., Woitek, R., McLean, MA., et al.[2023]

In a study using hyperpolarized 13C MRI on nine mice with partial unilateral ureteral obstruction (pUUO), significant changes in metabolic markers were observed, indicating a shift towards glycolytic metabolism in both kidneys after obstruction.

The obstructed kidney showed increased lactate to pyruvate ratios, hydronephrosis, fibrosis, and macrophage infiltration, highlighting the injury and inflammation specific to that kidney, while the unobstructed kidney remained unaffected.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of renal metabolic response to partial ureteral obstruction with hyperpolarized 13 C MRI. Niles, DJ., Gordon, JW., Huang, G., et al.[2023]

Hyperpolarized 13C-pyruvate MRI successfully detected high rates of glycolytic metabolism in metastatic prostate cancer, with specific kPL values indicating metabolic activity in bone and liver metastases.

The study demonstrated that HP 13C-pyruvate MRI can measure changes in metabolism over time, showing a decrease in kPL values in response to chemotherapy, suggesting its potential as a tool for monitoring treatment efficacy in advanced prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperpolarized 13C-pyruvate MRI detects real-time metabolic flux in prostate cancer metastases to bone and liver: a clinical feasibility study. Chen, HY., Aggarwal, R., Bok, RA., et al.[2021]

Hyperpolarized 13C pyruvate MRI can noninvasively assess lactate production in renal tumors, which is linked to their aggressiveness, as shown in a study using mouse models of human renal cell carcinoma with varying LDHA and MCT4 expression.

The technique demonstrated that tumors with higher lactate production (A498) had greater pyruvate-to-lactate conversion and faster lactate export compared to less aggressive tumors, suggesting its potential to guide treatment decisions based on tumor behavior.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-Invasive Assessment of Lactate Production and Compartmentalization in Renal Cell Carcinomas Using Hyperpolarized 13C Pyruvate MRI. Sriram, R., Gordon, J., Baligand, C., et al.[2020]

Hyperpolarized (HP) 13C MRI offers a promising new method for imaging kidney structure and function, particularly in assessing renal metabolism, which could improve the diagnosis and monitoring of kidney diseases.

Preclinical studies using various metabolic probes, such as [1-13C]pyruvate, indicate that HP 13C MRI has significant potential for evaluating conditions like kidney cancer and diabetic nephropathy, although further research is needed to transition these findings into clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperpolarized Carbon (13C) MRI of the Kidneys: Basic Concept. von Morze, C., Reed, GD., Wang, ZJ., et al.[2022]

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]

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 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 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]

References

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

Hyperpolarized 13C-Pyruvate Metabolism as a Surrogate for Tumor Grade and Poor Outcome in Renal Cell Carcinoma-A Proof of Principle Study. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Evaluation of renal metabolic response to partial ureteral obstruction with hyperpolarized 13 C MRI. [2023]

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

Hyperpolarized 13C-pyruvate MRI detects real-time metabolic flux in prostate cancer metastases to bone and liver: a clinical feasibility study. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Non-Invasive Assessment of Lactate Production and Compartmentalization in Renal Cell Carcinomas Using Hyperpolarized 13C Pyruvate MRI. [2020]

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

Hyperpolarized Carbon (13C) MRI of the Kidneys: Basic Concept. [2022]

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

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

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

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

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

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

9. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

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