Hyperpolarized Pyruvate Imaging for Cancer
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Memorial Sloan Kettering Cancer Center
Disqualifiers: Breastfeeding, Claustrophobia, Hepatic, Renal, others
No Placebo Group
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?The purpose of the study is to test a new approach to see if the test results can be reproduced each time the Magnetic resonance imaging (MRI) is done for an individual patient. The study will explore the use of an imaging agent called hyperpolarized \[1-13C\] pyruvate (HP) with MRI scans. (MRI) is a technique that takes pictures of the body's organs using a magnetic field and radiofrequency waves that cannot be felt. In order to accomplish the goal of the study the patient will have two hyperpolarized MRI scans to assess if scans can be reproduced. The hyperpolarized MRI scans will be compared with the pathological results of the surgery to see if the hyperpolarized MRI provides additional information regarding disease metabolism.
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 trial coordinators or your doctor.
What data supports the effectiveness of the treatment Hyperpolarized Pyruvate Imaging for Cancer?
Research shows that hyperpolarized pyruvate imaging can help track cancer metabolism by highlighting how cancer cells process energy differently, which can be useful for early detection and monitoring treatment response. Studies in breast cancer have demonstrated that this imaging technique can identify changes in tumor metabolism before structural changes occur, potentially allowing for earlier intervention.
12345Is hyperpolarized pyruvate imaging safe for humans?
The research on hyperpolarized pyruvate imaging, particularly in cancer studies, suggests it is generally safe for use in humans. Clinical feasibility has been demonstrated in breast cancer patients, and the technique is being explored for its potential in metabolic imaging without reported safety concerns.
13678How does hyperpolarized pyruvate imaging differ from other cancer treatments?
Hyperpolarized pyruvate imaging is unique because it uses a special form of MRI to track the metabolism of cancer cells in real-time, providing detailed insights into tumor activity. This method enhances the detection sensitivity by thousands of times, allowing for early identification of treatment responses, unlike traditional imaging techniques.
1791011Eligibility Criteria
This trial is for patients with certain cancers (sarcoma, prostate, breast, brain, metastatic or pancreatic) who can undergo MRI scans. They must not be pregnant or breastfeeding and should have a tumor that's measurable. People with severe liver or kidney issues, major illnesses like unstable heart conditions, or those who cannot tolerate an MRI due to devices like pacemakers are excluded.Inclusion Criteria
My cancer diagnosis was confirmed by a pathology department, or I have suspected brain cancer based on MRI.
My cancer can be measured or seen on scans, with a tumor larger than 1cm.
I am not pregnant, confirmed by a recent test.
+1 more
Exclusion Criteria
Standard MRI exclusion criteria will also be applied, including pacemakers and metal clips located in the patient
I cannot or will not have an IV line placed for a pyruvate injection.
I do not have any severe illnesses like heart problems.
+4 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Imaging
Participants undergo two hyperpolarized MRI scans to assess reproducibility
1-2 weeks
2 visits (in-person)
Follow-up
Participants are monitored for safety and effectiveness after imaging
4 weeks
Participant Groups
The study tests the reliability of hyperpolarized [1-13C] pyruvate (HP) in MRI scans for cancer patients by conducting two HP-MRI scans to see if they produce consistent results each time. It also compares these images with surgical pathology to check if it offers extra details on disease metabolism.
1Treatment groups
Experimental Treatment
Group I: Hyperpolarized Pyruvate MRI ReproducibilityExperimental Treatment1 Intervention
This is a reproducibility study of hyperpolarized \[1-13C\] pyruvate MRI in patients with solid tumors. A total of 100 patients will be enrolled, 50 of whom will be imaged using 1D MR spectroscopy and the other 50 with 3D imaging sequence.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Memorial Sloan Kettering Bergen (Consent only )Montvale, NJ
Memorial Sloan Kettering Cancer CenterNew York, NY
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Who Is Running the Clinical Trial?
Memorial Sloan Kettering Cancer CenterLead Sponsor
References
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.
Combined hyperpolarized 13C-pyruvate MRS and 18F-FDG PET (hyperPET) estimates of glycolysis in canine cancer patients. [2019]13C Magnetic Resonance Spectroscopy (MRS) using hyperpolarized 13C-labeled pyruvate as a substrate offers a measure of pyruvate-lactate interconversion and is thereby a marker of the elevated aerobic glycolysis (Warburg effect) generally exhibited by cancer cells. Here, we aim to compare hyperpolarized [1-13C]pyruvate MRS with simultaneous 18F-2-fluoro-2-deoxy-d-glucose (FDG) PET in a cross-sectional study of canine cancer patients.
Hyperpolarised 13C-MRI using 13C-pyruvate in breast cancer: A review. [2023]Tumour metabolism can be imaged with a novel imaging technique termed hyperpolarised carbon-13 (13C)-MRI using probes, i.e., endogenously found molecules that are labeled with 13C. Hyperpolarisation of the 13C label increases the sensitivity to a level that allows dynamic imaging of the distribution and metabolism of the probes. Dynamic imaging of [1-13C]pyruvate metabolism is of particular biological interest in cancer because of the Warburg effect resulting in the intratumoural accumulation of [1-13C]pyruvate and conversion to [1-13C]lactate. Numerous preclinical studies in breast cancer and other tumours have shown that hyperpolarised 13C-pyruvate has potential for metabolic phenotyping and response assessment at earlier timepoints than the current clinical imaging techniques allow. The clinical feasibility of hyperpolarised 13C-MRI after the injection of pyruvate in patients with breast cancer has now been demonstrated, with increased 13C-label exchange between pyruvate and lactate present in higher grade tumours with associated increased expression of the monocarboxylate transporter 1 (MCT1), the transmembrane transporter mediating intracellular pyruvate uptake, and lactate dehydrogenase (LDH) as the enzyme catalysing the conversion of pyruvate to lactate. Furthermore, a study in patients with breast cancer undergoing neoadjuvant chemotherapy suggested that early changes in 13C-label exchange can distinguish between patients who reach pathologic complete response (pCR) and those who do not. This review summarises the current literature on preclinical and clinical research on hyperpolarised 13C-MRI with [1-13C]-pyruvate in breast cancer imaging.
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.
Dynamic nuclear polarisation: The future of imaging in oncology? [2020]As clinical oncology evolves with new treatment options becoming available, there is an increasing demand on anatomic imaging for the assessment of patients at different stages. Imaging with hyperpolarized 13C-labelled cell substrates has the potential to become a powerful tool in many steps of clinical evaluation, offering a new metabolic metric and therefore a more personalised approach to treatment response. This articles explores the metabolic basis and potential for translation of hyperpolarised pyruvate as a dynamic nuclear polarisation probe in clinical oncology.
Hyperpolarized 13carbon MR. [2019]Hyperpolarized (HP) (13)C labeled compounds can be used as MR contrast agents to investigate metabolic pathways in vivo in almost real time. To date, a high proportion of reported studies have utilized HP 1-(13)C pyruvate to investigate intracellular metabolism in tumors and other tissues. The long T(1) relaxation time of the carboxylate carbon enables the (13)C signal of the pyruvate to be followed for nearly 2 minutes following injection. During this time, pyruvate is rapidly metabolized to generate observable metabolites such as alanine and lactate. HP (13)C labeled compounds have, for example, also been used to non-invasively probe physiological parameters such as pH, which emphasizes the expanding potential of the technique. The commercial availability of dynamic nuclear polarization (DNP) systems to generate hyperpolarized material for injection has made the technique available to researchers worldwide. As a consequence, DNP (13)C MR has become a rapidly expanding area of research. The technique, with its specific strengths and weaknesses, has incredible potential coupled with inherent limitations, and this review aims to both present background to the technique and describe some of the necessary hardware and software essential to perform hyperpolarized (13)C studies. An overview of the current and future role of HP (13)C based molecular imaging is presented.
Real-Time Pyruvate Chemical Conversion Monitoring Enabled by PHIP. [2023]In recent years, parahydrogen-induced polarization side arm hydrogenation (PHIP-SAH) has been applied to hyperpolarize [1-13C]pyruvate and map its metabolic conversion to [1-13C]lactate in cancer cells. Developing on our recent MINERVA pulse sequence protocol, in which we have achieved 27% [1-13C]pyruvate carbon polarization, we demonstrate the hyperpolarization of [1,2-13C]pyruvate (∼7% polarization on each 13C spin) via PHIP-SAH. By altering a single parameter in the pulse sequence, MINERVA enables the signal enhancement of C1 and/or C2 in [1,2-13C]pyruvate with the opposite phase, which allows for the simultaneous monitoring of different chemical reactions with enhanced spectral contrast or for the same reaction via different carbon sites. We first demonstrate the ability to monitor the same enzymatic pyruvate to lactate conversion at 7T in an aqueous solution, in vitro, and in-cell (HeLa cells) via different carbon sites. In a second set of experiments, we use the C1 and C2 carbon positions as spectral probes for simultaneous chemical reactions: the production of acetate, carbon dioxide, bicarbonate, and carbonate by reacting [1,2-13C]pyruvate with H2O2 at a high temperature (55 °C). Importantly, we detect and characterize the intermediate 2-hydroperoxy-2-hydroxypropanoate in real time and at high temperature.
Metabolic Studies of Tumor Cells Using [1-13 C] Pyruvate Hyperpolarized by Means of PHIP-Side Arm Hydrogenation. [2019]The kinetics of metabolic processes can be assessed, in real time by means of MR hyperpolarized (HP) metabolites. [1-13 C]pyruvate, hyperpolarized by means of d-DNP, is, by far, the substrate most widely applied to the investigation of several pathologies characterized by deregulated glycolytic metabolic networks, including cancer. Hyperpolarization of [1-13 C]pyruvate by means of the cost effective, fast and easy to handle PHIP-SAH (para-hydrogen induced polarization-side arm hydrogenation) method opens-up a pathway for the application of HP metabolites to a wide range of cancer-related studies. Herein, we report the first application of PHIP-SAH hyperpolarized [1-13 C]pyruvate in the investigation of upregulated glycolysis in two murine breast cancer cell lines (168FARN and 4T1). The results obtained using HP pyruvate have been validated with a conventional biochemical assay and are coherent with previously-reported lactate dehydrogenase activity measured in those cells.
Hyperpolarized 13C MRI: State of the Art and Future Directions. [2020]Hyperpolarized (HP) carbon 13 (13C) MRI is an emerging molecular imaging method that allows rapid, noninvasive, and pathway-specific investigation of dynamic metabolic and physiologic processes that were previously inaccessible to imaging. This technique has enabled real-time in vivo investigations of metabolism that are central to a variety of diseases, including cancer, cardiovascular disease, and metabolic diseases of the liver and kidney. This review provides an overview of the methods of hyperpolarization and 13C probes investigated to date in preclinical models of disease. The article then discusses the progress that has been made in translating this technology for clinical investigation. In particular, the potential roles and emerging clinical applications of HP [1-13C]pyruvate MRI will be highlighted. The future directions to enable the adoption of this technology to advance the basic understanding of metabolism, to improve disease diagnosis, and to accelerate treatment assessment are also detailed.
Kinetic analysis of multi-resolution hyperpolarized 13 C human brain MRI to study cerebral metabolism. [2023]Label="PURPOSE">To investigate multi-resolution hyperpolarized (HP) 13 C pyruvate MRI for measuring kinetic conversion rates in the human brain.
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.