HP C13-aKG MRI for Brain Tumor
Recruiting in Palo Alto (17 mi)
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.
12345Is 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.
12567What 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.
12348Eligibility 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.
+14 more
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)
Participant Groups
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.
2Treatment groups
Experimental Treatment
Group I: Cohort 2: Hyperpolarized Carbon-13 Alpha-ketoglutarate (HP 13C-aKG)Experimental Treatment2 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 Treatment2 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.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of California, San FranciscoSan Francisco, CA
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Who Is Running the Clinical Trial?
Robert Bok, MD, PhDLead Sponsor
National Cancer Institute (NCI)Collaborator
References
Pilot Study of Hyperpolarized 13C Metabolic Imaging in Pediatric Patients with Diffuse Intrinsic Pontine Glioma and Other CNS Cancers. [2022]Label="BACKGROUND AND PURPOSE">Pediatric CNS tumors commonly present challenges for radiographic interpretation on conventional MR imaging. This study sought to investigate the safety and tolerability of hyperpolarized carbon-13 (HP-13C) metabolic imaging in pediatric patients with brain tumors.
Characterization of serial hyperpolarized 13C metabolic imaging in patients with glioma. [2021]Label="BACKGROUND">Hyperpolarized carbon-13 (HP-13C) MRI is a non-invasive imaging technique for probing brain metabolism, which may improve clinical cancer surveillance. This work aimed to characterize the consistency of serial HP-13C imaging in patients undergoing treatment for brain tumors and determine whether there is evidence of aberrant metabolism in the tumor lesion compared to normal-appearing tissue.
Characterization of Distinctive In Vivo Metabolism between Enhancing and Non-Enhancing Gliomas Using Hyperpolarized Carbon-13 MRI. [2021]The development of hyperpolarized carbon-13 (13C) metabolic MRI has enabled the sensitive and noninvasive assessment of real-time in vivo metabolism in tumors. Although several studies have explored the feasibility of using hyperpolarized 13C metabolic imaging for neuro-oncology applications, most of these studies utilized high-grade enhancing tumors, and little is known about hyperpolarized 13C metabolic features of a non-enhancing tumor. In this study, 13C MR spectroscopic imaging with hyperpolarized [1-13C]pyruvate was applied for the differential characterization of metabolic profiles between enhancing and non-enhancing gliomas using rodent models of glioblastoma and a diffuse midline glioma. Distinct metabolic profiles were found between the enhancing and non-enhancing tumors, as well as their contralateral normal-appearing brain tissues. The preliminary results from this study suggest that the characterization of metabolic patterns from hyperpolarized 13C imaging between non-enhancing and enhancing tumors may be beneficial not only for understanding distinct metabolic features between the two lesions, but also for providing a basis for understanding 13C metabolic processes in ongoing clinical trials with neuro-oncology patients using this technology.
Towards hyperpolarized (13)C-succinate imaging of brain cancer. [2018]We describe a novel (13)C enriched precursor molecule, sodium 1-(13)C acetylenedicarboxylate, which after hydrogenation by PASADENA (Parahydrogen and Synthesis Allows Dramatically Enhanced Nuclear Alignment) under controlled experimental conditions, becomes hyperpolarized (13)C sodium succinate. Fast in vivo 3D FIESTA MR imaging demonstrated that, following carotid arterial injection, the hyperpolarized (13)C-succinate appeared in the head and cerebral circulation of normal and tumor-bearing rats. At this time, no in vivo hyperpolarized signal has been localized to normal brain or brain tumor. On the other hand, ex vivo samples of brain harvested from rats bearing a 9L brain tumor, 1 h or more following in vivo carotid injection of hyperpolarized (13)C sodium succinate, contained significant concentrations of the injected substrate, (13)C sodium succinate, together with (13)C maleate and succinate metabolites 1-(13)C-glutamate, 5-(13)C-glutamate, 1-(13)C-glutamine and 5-(13)C-glutamine. The (13)C substrates and products were below the limits of NMR detection in ex vivo samples of normal brain consistent with an intact blood-brain barrier. These ex vivo results indicate that hyperpolarized (13)C sodium succinate may become a useful tool for rapid in vivo identification of brain tumors, providing novel biomarkers in (13)C MR spectral-spatial images.
Simple Esterification of [1-13C]-Alpha-Ketoglutarate Enhances Membrane Permeability and Allows for Noninvasive Tracing of Glutamate and Glutamine Production. [2023]Alpha-ketoglutarate (α-KG) is a key metabolite and signaling molecule in cancer cells, but the low permeability of α-KG limits the study of α-KG mediated effects in vivo. Recently, cell-permeable monoester and diester α-KG derivatives have been synthesized for use in vivo, but many of these derivatives are not compatible for use in hyperpolarized carbon-13 nuclear magnetic resonance spectroscopy (HP-13C-MRS). HP-13C-MRS is a powerful technique that has been used to noninvasively trace labeled metabolites in real time. Here, we show that using diethyl-[1-13C]-α-KG as a probe in HP-13C-MRS allows for noninvasive tracing of α-KG metabolism in vivo.
Rapid 13C Hyperpolarization of the TCA Cycle Intermediate α-Ketoglutarate via SABRE-SHEATH. [2023]α-Ketoglutarate is a key biomolecule involved in a number of metabolic pathways─most notably the TCA cycle. Abnormal α-ketoglutarate metabolism has also been linked with cancer. Here, isotopic labeling was employed to synthesize [1-13C,5-12C,D4]α-ketoglutarate with the future goal of utilizing its [1-13C]-hyperpolarized state for real-time metabolic imaging of α-ketoglutarate analytes and its downstream metabolites in vivo. The signal amplification by reversible exchange in shield enables alignment transfer to heteronuclei (SABRE-SHEATH) hyperpolarization technique was used to create 9.7% [1-13C] polarization in 1 minute in this isotopologue. The efficient 13C hyperpolarization, which utilizes parahydrogen as the source of nuclear spin order, is also supported by favorable relaxation dynamics at 0.4 μT field (the optimal polarization transfer field): the exponential 13C polarization buildup constant Tb is 11.0 ± 0.4 s whereas the 13C polarization decay constant T1 is 18.5 ± 0.7 s. An even higher 13C polarization value of 17.3% was achieved using natural-abundance α-ketoglutarate disodium salt, with overall similar relaxation dynamics at 0.4 μT field, indicating that substrate deuteration leads only to a slight increase (∼1.2-fold) in the relaxation rates for 13C nuclei separated by three chemical bonds. Instead, the gain in polarization (natural abundance versus [1-13C]-labeled) is rationalized through the smaller heat capacity of the "spin bath" comprising available 13C spins that must be hyperpolarized by the same number of parahydrogen present in each sample, in line with previous 15N SABRE-SHEATH studies. Remarkably, the C-2 carbon was not hyperpolarized in both α-ketoglutarate isotopologues studied; this observation is in sharp contrast with previously reported SABRE-SHEATH pyruvate studies, indicating that the catalyst-binding dynamics of C-2 in α-ketoglutarate differ from that in pyruvate. We also demonstrate that 13C spectroscopic characterization of α-ketoglutarate and pyruvate analytes can be performed at natural 13C abundance with an estimated detection limit of 80 micromolar concentration × *%P13C. All in all, the fundamental studies reported here enable a wide range of research communities with a new hyperpolarized contrast agent potentially useful for metabolic imaging of brain function, cancer, and other metabolically challenging diseases.
Synthesis of [1-13 C-5-12 C]-alpha-ketoglutarate enables noninvasive detection of 2-hydroxyglutarate. [2023]Isocitrate dehydrogenase 1 (IDH1) mutations that generate the oncometabolite 2-hydroxyglutarate (2-HG) from α-ketoglutarate (α-KG) have been identified in many types of tumors and are an important prognostic factor in gliomas. 2-HG production can be determined by hyperpolarized carbon-13 magnetic resonance spectroscopy (HP-13 C-MRS) using [1-13 C]-α-KG as a probe, but peak contamination from naturally occurring [5-13 C]-α-KG overlaps with the [1-13 C]-2-HG peak. Via a newly developed oxidative-Stetter reaction, [1-13 C-5-12 C]-α-KG was synthesized. α-KG metabolism was measured via HP-13 C-MRS using [1-13 C-5-12 C]-α-KG as a probe. [1-13 C-5-12 C]-α-KG was synthesized in high yields, and successfully eliminated the signal from C5 of α-KG in the HP-13 C-MRS spectra. In HCT116 IDH1 R132H cells, [1-13 C-5-12 C]-α-KG allowed for unimpeded detection of [1-13 C]-2-HG. 12 C-enrichment represents a novel method to circumvent spectral overlap, and [1-13 C-5-12 C]-α-KG shows promise as a probe to study IDH1 mutant tumors and α-KG metabolism.
Hyperpolarized 13C MRI: Path to Clinical Translation in Oncology. [2023]This white paper discusses prospects for advancing hyperpolarization technology to better understand cancer metabolism, identify current obstacles to HP (hyperpolarized) 13C magnetic resonance imaging's (MRI's) widespread clinical use, and provide recommendations for overcoming them. Since the publication of the first NIH white paper on hyperpolarized 13C MRI in 2011, preclinical studies involving [1-13C]pyruvate as well a number of other 13C labeled metabolic substrates have demonstrated this technology's capacity to provide unique metabolic information. A dose-ranging study of HP [1-13C]pyruvate in patients with prostate cancer established safety and feasibility of this technique. Additional studies are ongoing in prostate, brain, breast, liver, cervical, and ovarian cancer. Technology for generating and delivering hyperpolarized agents has evolved, and new MR data acquisition sequences and improved MRI hardware have been developed. It will be important to continue investigation and development of existing and new probes in animal models. Improved polarization technology, efficient radiofrequency coils, and reliable pulse sequences are all important objectives to enable exploration of the technology in healthy control subjects and patient populations. It will be critical to determine how HP 13C MRI might fill existing needs in current clinical research and practice, and complement existing metabolic imaging modalities. Financial sponsorship and integration of academia, industry, and government efforts will be important factors in translating the technology for clinical research in oncology. This white paper is intended to provide recommendations with this goal in mind.