HP C13-aKG MRI for Brain Tumor

Overseen by Susan Chang, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Recruiting

Sponsor: Robert Bok, MD, PhD

Disqualifiers: Congestive heart failure, Myocardial infarction, HIV, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial uses a special imaging dye to help doctors see brain tumors more clearly on MRI scans. It focuses on patients with a specific type of brain tumor that may not respond well to typical treatments. The dye makes the tumors more visible, aiding in better measurement and understanding.

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 data supports the effectiveness of the treatment Hyperpolarized Carbon 13 Alpha-ketoglutarate (HP C13-aKG) for brain tumors?

The research suggests that hyperpolarized carbon-13 MRI, a technique used in the treatment, can help identify and understand the metabolism of brain tumors, which may improve cancer monitoring and treatment planning. Additionally, studies have shown that hyperpolarized carbon-13 imaging can differentiate between different types of brain tumors, potentially aiding in more accurate diagnosis and treatment strategies. ^{1 2 3 4 5}

Is Hyperpolarized Carbon 13 Alpha-ketoglutarate (HP C13-aKG) safe for use in humans?

A pilot study on hyperpolarized carbon-13 metabolic imaging in pediatric patients with brain tumors found it to be safe and well-tolerated, suggesting it is generally safe for human use. ^{1 2 5 6 7}

What makes the treatment HP C13-aKG MRI for brain tumors unique?

HP C13-aKG MRI is unique because it uses a special imaging technique that allows doctors to see real-time metabolism in brain tumors, which can help in understanding the tumor's behavior and potentially improve monitoring and treatment decisions. ^{1 2 3 4 8}

Research Team

Susan Chang, MD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

This trial is for adults over 18 with IDH mutant glioma brain tumors. They must have good kidney function, no severe medical illnesses, heart failure, recent heart attacks or unstable angina. Life expectancy should be more than 8 weeks and a performance status indicating they can carry out daily activities. Pregnant or breastfeeding women are excluded, as well as those with other cancers unless in remission for 3+ years.

Inclusion Criteria

I do not have serious heart failure.

I do not have HIV.

My glioma has recurred and has an IDH mutation, and I haven't had surgery yet.

Exclusion Criteria

Participants unable to comply with study procedures

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Imaging

Participants receive a single MR scan with the administration of HP 13C-aKG to evaluate tumor burden

1 day

1 visit (in-person)

Follow-up

Participants receive a follow-up phone call to assess for late adverse events

1 week

1 call (virtual)

Treatment Details

Interventions

• Hyperpolarized Carbon 13 Alpha-ketoglutarate (HP C13-aKG) (Metabolic Imaging Agent)
• Magnetic Resonance Image (MRI) (Procedure)

Trial Overview The study tests a new imaging technique using Hyperpolarized Carbon-13 Alpha-ketoglutarate (HP C13-aKG) alongside MRI to assess tumor burden in patients with specific brain tumors. It aims to improve how we visualize the size and location of these tumors.

Participant Groups

Group I: Cohort 2: Hyperpolarized Carbon-13 Alpha-ketoglutarate (HP 13C-aKG) Experimental Treatment 2 Interventions

Cohort 2 will be comprised 30 participants with recurrent IDH mutant glioma before receiving surgical resection. Participants will be injected with 0.67ml/kg actual body weight of 100 millimolar (mM) of α-KG solution and have a single imaging scan.

Group II: Cohort 1: Hyperpolarized Carbon-13 Alpha-ketoglutarate (HP 13C-aKG) Experimental Treatment 2 Interventions

Cohort 1 will be comprised of 10 participants with Isocitrate dehydrogenase (IDH) mutant glioma who may or may not have received prior treatment for optimizing imaging protocol. Participants will be injected with 0.67ml/kg actual body weight of 100 millimolar (mM) of α-KG solution and have a single imaging scan.

Who Is Running the Clinical Trial?

Robert Bok, MD, PhD

Lead Sponsor

Trials

3

Recruited

270+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

The study demonstrated that hyperpolarized carbon-13 (HP-13C) metabolic imaging is safe and well-tolerated in pediatric patients with brain tumors, with no adverse events reported during the imaging process.

HP-13C imaging successfully showed the brain's metabolism of HP [1-13C]pyruvate, indicating its potential as a useful tool for assessing metabolic changes in pediatric CNS tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot Study of Hyperpolarized 13C Metabolic Imaging in Pediatric Patients with Diffuse Intrinsic Pontine Glioma and Other CNS Cancers. Autry, AW., Park, I., Kline, C., et al.[2022]

Hyperpolarized carbon-13 MRI (HP-13C MRI) showed consistent measurements of brain metabolism in both healthy volunteers and patients with diffuse infiltrating glioma, indicating its potential as a reliable non-invasive imaging technique for monitoring brain tumor treatment.

In patients treated with the anti-angiogenic agent bevacizumab, there were significant increases in metabolic rates (kPL and kPB) in normal-appearing white matter, while progressive disease was associated with elevated kPL in tumor lesions, suggesting that HP-13C MRI can detect metabolic changes related to tumor progression and treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of serial hyperpolarized 13C metabolic imaging in patients with glioma. Autry, AW., Gordon, JW., Chen, HY., et al.[2021]

Hyperpolarized carbon-13 (13C) metabolic MRI can effectively differentiate between enhancing and non-enhancing gliomas by revealing distinct metabolic profiles, as demonstrated in rodent models of glioblastoma and diffuse midline glioma.

The study's findings suggest that understanding these metabolic differences could enhance our knowledge of tumor biology and support ongoing clinical trials using hyperpolarized 13C imaging in neuro-oncology patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of Distinctive In Vivo Metabolism between Enhancing and Non-Enhancing Gliomas Using Hyperpolarized Carbon-13 MRI. Park, S., Rintaro, H., Kim, SK., et al.[2021]

A new (13)C enriched molecule, sodium 1-(13)C acetylenedicarboxylate, can be converted into hyperpolarized (13)C sodium succinate, which shows potential for imaging brain tumors using advanced MR techniques.

In studies with rats, while the hyperpolarized (13)C-succinate did not localize to the brain during imaging, significant amounts were found in tumor tissue after injection, suggesting it could serve as a biomarker for identifying brain tumors in future applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Towards hyperpolarized (13)C-succinate imaging of brain cancer. Bhattacharya, P., Chekmenev, EY., Perman, WH., et al.[2018]

Diethyl-[1-13C]-α-ketoglutarate (α-KG) has been developed as a cell-permeable probe that enables the noninvasive tracing of α-KG metabolism in living organisms using hyperpolarized carbon-13 nuclear magnetic resonance spectroscopy (HP-13C-MRS).

This advancement allows researchers to study the effects of α-KG in cancer cells more effectively, overcoming the limitations of α-KG's low permeability and enhancing our understanding of its role as a signaling molecule in vivo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simple Esterification of [1-13C]-Alpha-Ketoglutarate Enhances Membrane Permeability and Allows for Noninvasive Tracing of Glutamate and Glutamine Production. AbuSalim, JE., Yamamoto, K., Miura, N., et al.[2023]

The study successfully synthesized hyperpolarized [1-13C]α-ketoglutarate, achieving a polarization of 9.7% in just one minute, which can be used for real-time metabolic imaging of α-ketoglutarate and its metabolites in living organisms.

The research highlights that the hyperpolarization dynamics of α-ketoglutarate differ from those of pyruvate, particularly noting that the C-2 carbon was not hyperpolarized, suggesting unique catalyst-binding behaviors that could impact its application in metabolic imaging for conditions like cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid 13C Hyperpolarization of the TCA Cycle Intermediate &#945;-Ketoglutarate via SABRE-SHEATH. Adelabu, I., Ettedgui, J., Joshi, SM., et al.[2023]

A new probe, [1-13C-5-12C]-α-KG, was developed to improve the detection of the oncometabolite 2-hydroxyglutarate (2-HG) in tumors with IDH1 mutations, allowing for clearer analysis of α-ketoglutarate metabolism.

This innovative method using hyperpolarized carbon-13 magnetic resonance spectroscopy (HP-13C-MRS) successfully eliminated signal interference, enhancing the ability to study IDH1 mutant tumors and potentially improving prognostic assessments in gliomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis of [1-13 C-5-12 C]-alpha-ketoglutarate enables noninvasive detection of 2-hydroxyglutarate. Miura, N., Mushti, C., Sail, D., 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]

References

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

Pilot Study of Hyperpolarized 13C Metabolic Imaging in Pediatric Patients with Diffuse Intrinsic Pontine Glioma and Other CNS Cancers. [2022]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Characterization of serial hyperpolarized 13C metabolic imaging in patients with glioma. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Characterization of Distinctive In Vivo Metabolism between Enhancing and Non-Enhancing Gliomas Using Hyperpolarized Carbon-13 MRI. [2021]

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

Towards hyperpolarized (13)C-succinate imaging of brain cancer. [2018]

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

Simple Esterification of [1-13C]-Alpha-Ketoglutarate Enhances Membrane Permeability and Allows for Noninvasive Tracing of Glutamate and Glutamine Production. [2023]

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

Rapid 13C Hyperpolarization of the TCA Cycle Intermediate &#945;-Ketoglutarate via SABRE-SHEATH. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Synthesis of [1-13 C-5-12 C]-alpha-ketoglutarate enables noninvasive detection of 2-hydroxyglutarate. [2023]

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

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