Trial Summary
What is the purpose of this trial?This pilot trial studies the side effects of hyperpolarized carbon C 13 pyruvate magnetic resonance imaging (MRI) in diagnosing participants with glioma. Diagnostic procedures, such as hyperpolarized carbon C 13 pyruvate MRI, may help find and diagnose glioma.
Do I need to stop my current medications for the trial?
The trial protocol does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.
What data supports the effectiveness of the treatment Hyperpolarized Carbon C 13 Pyruvate for brain tumors?
Research shows that hyperpolarized Carbon C 13 Pyruvate can help detect treatment responses in brain tumors by tracking changes in tumor metabolism, which is useful for early identification of treatment effectiveness. This method has been effective in other cancers, like breast cancer, by providing detailed metabolic information that can guide treatment decisions.
12345Is hyperpolarized MRI using carbon-13 pyruvate safe for humans?
Research indicates that hyperpolarized carbon-13 pyruvate MRI has been safely used in humans, including healthy volunteers and pediatric patients with brain tumors, without reported adverse effects.
12678How does the treatment Hyperpolarized MRI for Brain Tumor differ from other treatments for this condition?
Hyperpolarized MRI for brain tumors is unique because it uses a special form of MRI with hyperpolarized carbon-13 pyruvate to visualize and measure the metabolism of brain tumors in real-time. This method provides detailed metabolic information that can help assess tumor activity and response to treatment, which is not possible with standard imaging techniques.
124910Eligibility Criteria
This trial is for adults over 18 with a life expectancy of more than 12 weeks and diagnosed with glioma, who are not HIV-positive, pregnant or breastfeeding. Participants must have adequate kidney function, no severe heart failure or recent heart attacks, and no other cancers except certain skin cancers or cervical carcinoma in-situ unless in remission for at least 3 years.Inclusion Criteria
I am over 18 years old and expected to live more than 12 weeks.
Patients must sign an informed consent indicating that they are aware of the investigational nature of this study. Patients must sign an authorization for the release of their protected health information.
I don't have any severe illnesses that would interfere with the study's imaging tests.
+10 more
Exclusion Criteria
Subjects must be excluded from participating in this study if they are not able to comply with study and/or follow-up procedures.
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Imaging and Injection
Participants receive one or two hyperpolarized carbon C 13 pyruvate injections intravenously and undergo MRI
1 day
1 visit (in-person)
Treatment
Participants in Cohort II receive standard radiation and temozolomide treatment outside of this study
Varies based on standard treatment protocols
Post-Treatment Imaging
Participants in Cohort II undergo MRI 4 weeks after completion of cancer therapy
1 day
1 visit (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
Up to 24 months
Participant Groups
The trial tests the safety of using hyperpolarized carbon C 13 pyruvate MRI to diagnose gliomas. It involves patients already scheduled for standard treatment with radiation and temozolomide (Cohort 2), as well as those with evaluable disease based on prior MR scans (Cohort 1).
2Treatment groups
Experimental Treatment
Group I: Cohort II (Hyperpolarized C13, MRI)Experimental Treatment4 Interventions
Participants receive hyperpolarized carbon C 13 pyruvate IV and undergo MRI before treatment and 4 weeks after completion of cancer therapy given outside of this study.
Group II: Cohort I (Hyperpolarized C13, MRI)Experimental Treatment2 Interventions
Participants receive hyperpolarized carbon C 13 pyruvate intravenously IV and undergo MRI. The second hyperpolarized 13 C injection/imaging will be started approximately 15 to 60 minutes after the first injection for those who are willing to receive two 13 C injections
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?
Susan ChangLead Sponsor
National Cancer Institute (NCI)Collaborator
References
Detecting response of rat C6 glioma tumors to radiotherapy using hyperpolarized [1- 13C]pyruvate and 13C magnetic resonance spectroscopic imaging. [2021]We show here that hyperpolarized [1-(13) C]pyruvate can be used to detect treatment response in a glioma tumor model; a tumor type where detection of response with (18) fluoro-2-deoxyglucose, using positron emission tomography, is limited by the high background signals from normal brain tissue. (13) C chemical shift images acquired following intravenous injection of hyperpolarized [1-(13) C]pyruvate into rats with implanted C6 gliomas showed significant labeling of lactate within the tumors but comparatively low levels in surrounding brain.Labeled pyruvate was observed at high levels in blood vessels above the brain and from other major vessels elsewhere but was detected at only low levels in tumor and brain.The ratio of hyperpolarized (13) C label in tumor lactate compared to the maximum pyruvate signal in the blood vessels was decreased from 0.38 ± 0.16 to 0.23 ± 0.13, (a reduction of 34%) by 72 h following whole brain irradiation with 15 Gy.
Hyperpolarized [2-13C]pyruvate MR molecular imaging with whole brain coverage. [2023]Hyperpolarized (HP) 13C Magnetic Resonance Imaging (MRI) was applied for the first time to image and quantify the uptake and metabolism of [2-13C]pyruvate in the human brain to provide new metabolic information on cerebral energy metabolism. HP [2-13C]pyruvate was injected intravenously and imaged in 5 healthy human volunteer exams with whole brain coverage in a 1-minute acquisition using a specialized spectral-spatial multi-slice echoplanar imaging (EPI) pulse sequence to acquire 13C-labeled volumetric and dynamic images of [2-13C]pyruvate and downstream metabolites [5-13C]glutamate and [2-13C]lactate. Metabolic ratios and apparent conversion rates of pyruvate-to-lactate (kPL) and pyruvate-to-glutamate (kPG) were quantified to investigate simultaneously glycolytic and oxidative metabolism in a single injection.
Preoperative imaging of glioblastoma patients using hyperpolarized 13C pyruvate: Potential role in clinical decision making. [2022]Label="BACKGROUND" NlmCategory="BACKGROUND">Glioblastoma remains incurable despite treatment with surgery, radiation therapy, and cytotoxic chemotherapy, prompting the search for a metabolic pathway unique to glioblastoma cells.13C MR spectroscopic imaging with hyperpolarized pyruvate can demonstrate alterations in pyruvate metabolism in these tumors.
Hyperpolarized Carbon-13 MRI in Breast Cancer. [2023]One of the hallmarks of cancer is metabolic reprogramming, including high levels of aerobic glycolysis (the Warburg effect). Pyruvate is a product of glucose metabolism, and 13C-MR imaging of the metabolism of hyperpolarized (HP) [1-13C]pyruvate (HP 13C-MRI) has been shown to be a potentially versatile tool for the clinical evaluation of tumor metabolism. Hyperpolarization of the 13C nuclear spin can increase the sensitivity of detection by 4-5 orders of magnitude. Therefore, following intravenous injection, the location of hyperpolarized 13C-labeled pyruvate in the body and its subsequent metabolism can be tracked using 13C-MRI. Hyperpolarized [13C]urea and [1,4-13C2]fumarate are also likely to translate to the clinic in the near future as tools for imaging tissue perfusion and post-treatment tumor cell death, respectively. For clinical breast imaging, HP 13C-MRI can be combined with 1H-MRI to address the need for detailed anatomical imaging combined with improved functional tumor phenotyping and very early identification of patients not responding to standard and novel neoadjuvant treatments. If the technical complexity of the hyperpolarization process and the relatively high associated costs can be reduced, then hyperpolarized 13C-MRI has the potential to become more widely available for large-scale clinical trials.
Hyperpolarized Carbon 13 MRI: Clinical Applications and Future Directions in Oncology. [2023]Hyperpolarized carbon 13 MRI (13C MRI) is a novel imaging approach that can noninvasively probe tissue metabolism in both normal and pathologic tissues. The process of hyperpolarization increases the signal acquired by several orders of magnitude, allowing injected 13C-labeled molecules and their downstream metabolites to be imaged in vivo, thus providing real-time information on kinetics. To date, the most important reaction studied with hyperpolarized 13C MRI is exchange of the hyperpolarized 13C signal from injected [1-13C]pyruvate with the resident tissue lactate pool. Recent preclinical and human studies have shown the role of several biologic factors such as the lactate dehydrogenase enzyme, pyruvate transporter expression, and tissue hypoxia in generating the MRI signal from this reaction. Potential clinical applications of hyperpolarized 13C MRI in oncology include using metabolism to stratify tumors by grade, selecting therapeutic pathways based on tumor metabolic profiles, and detecting early treatment response through the imaging of shifts in metabolism that precede tumor structural changes. This review summarizes the foundations of hyperpolarized 13C MRI, presents key findings from human cancer studies, and explores the future clinical directions of the technique in oncology. Keywords: Hyperpolarized Carbon 13 MRI, Molecular Imaging, Cancer, Tissue Metabolism © RSNA, 2023.
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.
Metabolic imaging in the anesthetized rat brain using hyperpolarized [1-13C] pyruvate and [1-13C] ethyl pyruvate. [2021]Formulation, polarization, and dissolution conditions were developed to obtain a stable hyperpolarized solution of [1-(13)C]-ethyl pyruvate. A maximum tolerated concentration and injection rate were determined, and (13)C spectroscopic imaging was used to compare the uptake of hyperpolarized [1-(13)C]-ethyl pyruvate relative to hyperpolarized [1-(13)C]-pyruvate into anesthetized rat brain. Hyperpolarized [1-(13)C]-ethyl pyruvate and [1-(13)C]-pyruvate metabolic imaging in normal brain is demonstrated and quantified in this feasibility and range-finding study.
In Vivo Metabolic Imaging of [1-13 C]Pyruvate-d3 Hyperpolarized By Reversible Exchange With Parahydrogen. [2023]Metabolic magnetic resonance imaging (MRI) using hyperpolarized (HP) pyruvate is becoming a non-invasive technique for diagnosing, staging, and monitoring response to treatment in cancer and other diseases. The clinically established method for producing HP pyruvate, dissolution dynamic nuclear polarization, however, is rather complex and slow. Signal Amplification By Reversible Exchange (SABRE) is an ultra-fast and low-cost method based on fast chemical exchange. Here, for the first time, we demonstrate not only in vivo utility, but also metabolic MRI with SABRE. We present a novel routine to produce aqueous HP [1-13 C]pyruvate-d3 for injection in 6 minutes. The injected solution was sterile, non-toxic, pH neutral and contained ≈30 mM [1-13 C]pyruvate-d3 polarized to ≈11 % (residual 250 mM methanol and 20 μM catalyst). It was obtained by rapid solvent evaporation and metal filtering, which we detail in this manuscript. This achievement makes HP pyruvate MRI available to a wide biomedical community for fast metabolic imaging of living organisms.
Metabolic Imaging of the Human Brain with Hyperpolarized 13C Pyruvate Demonstrates 13C Lactate Production in Brain Tumor Patients. [2019]Hyperpolarized (HP) MRI using [1-13C] pyruvate is a novel method that can characterize energy metabolism in the human brain and brain tumors. Here, we present the first dynamically acquired human brain HP 13C metabolic spectra and spatial metabolite maps in cases of both untreated and recurrent tumors. In vivo production of HP lactate from HP pyruvate by tumors was indicative of altered cancer metabolism, whereas production of HP lactate in the entire brain was likely due to baseline metabolism. We correlated our results with standard clinical brain MRI, MRI DCE perfusion, and in one case FDG PET/CT. Our results suggest that HP 13C pyruvate-to-lactate conversion may be a viable metabolic biomarker for assessing tumor response.Significance: Hyperpolarized pyruvate MRI enables metabolic imaging in the brain and can be a quantitative biomarker for active tumors.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/14/3755/F1.large.jpg Cancer Res; 78(14); 3755-60. ©2018 AACR.
Imaging Glioblastoma Metabolism by Using Hyperpolarized [1-13C]Pyruvate Demonstrates Heterogeneity in Lactate Labeling: A Proof of Principle Study. [2022]Purpose To evaluate glioblastoma (GBM) metabolism by using hyperpolarized carbon 13 (13C) MRI to monitor the exchange of the hyperpolarized 13C label between injected [1-13C]pyruvate and tumor lactate and bicarbonate. Materials and Methods In this prospective study, seven treatment-naive patients (age [mean ± SD], 60 years ± 11; five men) with GBM were imaged at 3 T by using a dual-tuned 13C-hydrogen 1 head coil. Hyperpolarized [1-13C]pyruvate was injected, and signal was acquired by using a dynamic MRI spiral sequence. Metabolism was assessed within the tumor, in the normal-appearing brain parenchyma (NABP), and in healthy volunteers by using paired or unpaired t tests and a Wilcoxon signed rank test. The Spearman ρ correlation coefficient was used to correlate metabolite labeling with lactate dehydrogenase A (LDH-A) expression and some immunohistochemical markers. The Benjamini-Hochberg procedure was used to correct for multiple comparisons. Results The bicarbonate-to-pyruvate (BP) ratio was lower in the tumor than in the contralateral NABP (P < .01). The tumor lactate-to-pyruvate (LP) ratio was not different from that in the NABP (P = .38). The LP and BP ratios in the NABP were higher than those observed previously in healthy volunteers (P < .05). Tumor lactate and bicarbonate signal intensities were strongly correlated with the pyruvate signal intensity (ρ = 0.92, P < .001, and ρ = 0.66, P < .001, respectively), and the LP ratio was weakly correlated with LDH-A expression in biopsy samples (ρ = 0.43, P = .04). Conclusion Hyperpolarized 13C MRI demonstrated variation in lactate labeling in GBM, both within and between tumors. In contrast, bicarbonate labeling was consistently lower in tumors than in the surrounding NABP. Keywords: Hyperpolarized 13C MRI, Glioblastoma, Metabolism, Cancer, MRI, Neuro-oncology Supplemental material is available for this article. Published under a CC BY 4.0 license.