HP C13-aKG MRI for Brain Tumor

Overseen By Wendy Ma

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Robert Bok, MD, PhD

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

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

Compensation: Varies

Number of Visits: 2

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new imaging method using a special compound called Hyperpolarized Carbon 13 Alpha-ketoglutarate (HP C13-aKG) to better understand brain tumors known as IDH mutant gliomas. The trial aims to enhance the visibility of these tumors on scans, potentially aiding in treatment planning. People with IDH mutant glioma, whether previously treated or not, qualify for this trial, especially if previous MRIs show visible tumors. As an Early Phase 1 trial, this research focuses on understanding how this new imaging method works in people, offering participants a chance to contribute to groundbreaking advancements in brain tumor diagnostics.

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 method is safe for characterizing tumor burden in brain tumors?

Research has shown that hyperpolarized carbon-13 alpha-ketoglutarate (HP 13C-aKG) is being explored for imaging brain tumors. Limited safety information exists for humans, as this trial is in its early stages. Researchers are testing the treatment to determine its safety. Early trials typically focus on gathering initial safety data to ensure the treatment is well-tolerated. Although HP 13C-aKG has not been safely used for other conditions, participants will be closely monitored for any side effects during this phase of the study. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for brain tumors, like IDH mutant glioma, often involve surgery, radiation, and chemotherapy, which target tumor cells directly. But Hyperpolarized Carbon-13 Alpha-ketoglutarate (HP C13-aKG) works differently by enhancing MRI imaging to better visualize these tumors. Researchers are excited about this trial because the HP C13-aKG technique offers a novel way to assess the metabolic activity of brain tumors in real-time, potentially allowing for more precise treatment planning. This approach could help doctors see how aggressive a tumor is and tailor treatments more effectively, ultimately improving patient outcomes.

What evidence suggests that hyperpolarized carbon-13 alpha-ketoglutarate MRI is effective for characterizing tumor burden in IDH mutant glioma?

Research has shown that a special imaging tool called hyperpolarized carbon-13 alpha-ketoglutarate (HP C13-aKG) can help doctors see brain tumors more clearly, especially those with certain genetic changes called IDH mutations. These tumors exhibit unique metabolic changes that HP C13-aKG can highlight. This trial will study HP C13-aKG in two separate cohorts: one cohort will include participants with IDH mutant glioma to optimize the imaging protocol, and another cohort will include participants with recurrent IDH mutant glioma before surgical resection. Studies have found that this imaging method can track how these tumors respond to treatments targeting these mutations. This suggests that HP C13-aKG might help doctors better understand tumor behavior and treatment effectiveness in patients with IDH mutant glioma. Early evidence also suggests it could improve the accuracy of tumor assessments. ^{1 3 5 6 7}

Who Is on the Research Team?

Susan Chang, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

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

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

Interventions

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

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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 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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05851378

Hyperpolarized Carbon-13 Alpha-ketoglutarate Imaging in ... PRIMARY OBJECTIVES: I. To define the most appropriate imaging parameters for obtaining hyperpolarized 13C-aKG from participants with IDH mutant glioma.

2. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05851378/hyperpolarized-carbon-13-alpha-ketoglutarate-imaging-in-idh-mutant-glioma

Hyperpolarized Carbon-13 Alpha-ketoglutarate Imaging in ... Cohort 1: Participants with IDH mutant glioma who may or may not have received priortreatment · Cohort 2: Participants with recurrent IDH mutant ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40044455/

Clinical Translation of Hyperpolarized 13 C Metabolic Probes ... ... IDH-mutant gliomas together with example data to show the targeted, pathway-dependent function of these agents and their utility. Additional ...

4. academic.oup.com academic.oup.com/noa/article/5/1/vdad143/7337326

Monitoring response to a clinically relevant IDH inhibitor in ... Hyperpolarized MR spectroscopy-based metabolic imaging can assess response to IDH inhibitors. Importance of the Study. Mutant isocitrate ...

5. ajnr.org ajnr.org/highwire/filestream/119115/field_highwire_adjunct_files/0/ajnr.A8726_preprint_supplement.pdf

Clinical Translation of Hyperpolarized 13C Metabolic ... and IDH-mutant gliomas together with example data to show the targeted, pathway-dependent function of these agents and their utility ...

6. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT05851378

Hyperpolarized Carbon-13 Alpha-ketoglutarate Imaging in ... PRIMARY OBJECTIVES: To define the most appropriate imaging parameters for obtaining hyperpolarized 13C-aKG from participants with IDH mutant ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10681661/

Monitoring response to a clinically relevant IDH inhibitor in ... Hyperpolarized MR spectroscopy-based metabolic imaging can assess response to IDH inhibitors. Importance of the Study. Mutant isocitrate dehydrogenase (IDH) ...