Hyperpolarized Carbon Metabolic Imaging in Multiple Sclerosis

Summary

The main purpose of this study is to assess whether hyperpolarized carbon imaging in relapsing remitting multiple sclerosis (MS) patients can be used to predict response to anti-CD20 disease modifying therapy. Study procedures will include magnetic resonance imaging (MRI) assessments with a hyperpolarized pyruvate sequence, clinical assessment as well as blood markers of disease progression. This method of imaging utilizes the Warburg effect, where innate immune cells utilize a metabolic shift to glycolysis instead of oxidative phosphorylation. In pre-clinical data, increased hyperpolarized lactate production has been found to be associated with increased microglial/macrophage infiltration in the brain. Although hyperpolarized carbon imaging in humans has been established and used in the field of oncology, this will be one of the first applications of hyperpolarized carbon the study of neuroinflammation in humans. We predict that hyperpolarized carbon imaging may have the potential to monitor and evaluate neuroinflammation in MS, and in particular the innate immune activation state that plays a role in MS progression. This imaging method may provide non-invasive monitoring of disease progression and therapy response for MS patients.

Timeline

Start

2026-06-03

Primary completion

2029-12-01

Completion

2029-12-01

Publications

• Background Ohl K, Tenbrock K, Kipp M. Oxidative stress in multiple sclerosis: Central and peripheral mode of action. Exp Neurol. 2016 Mar;277:58-67. doi: 10.1016/j.expneurol.2015.11.010. Epub 2015 Nov 26.
• Background Golman K, in 't Zandt R, Thaning M. Real-time metabolic imaging. Proc Natl Acad Sci U S A. 2006 Jul 25;103(30):11270-5. doi: 10.1073/pnas.0601319103. Epub 2006 Jul 12.
• Background Nelson SJ, Kurhanewicz J, Vigneron DB, Larson PE, Harzstark AL, Ferrone M, van Criekinge M, Chang JW, Bok R, Park I, Reed G, Carvajal L, Small EJ, Munster P, Weinberg VK, Ardenkjaer-Larsen JH, Chen AP, Hurd RE, Odegardstuen LI, Robb FJ, Tropp J, Murray JA. Metabolic imaging of patients with prostate cancer using hyperpolarized [1-(1)(3)C]pyruvate. Sci Transl Med. 2013 Aug 14;5(198):198ra108. doi: 10.1126/scitranslmed.3006070.
• Background Tang S, Meng MV, Slater JB, Gordon JW, Vigneron DB, Stohr BA, Larson PEZ, Wang ZJ. Metabolic imaging with hyperpolarized 13 C pyruvate magnetic resonance imaging in patients with renal tumors-Initial experience. Cancer. 2021 Aug 1;127(15):2693-2704. doi: 10.1002/cncr.33554. Epub 2021 Apr 12.
• Background Park I, Larson PEZ, Gordon JW, Carvajal L, Chen HY, Bok R, Van Criekinge M, Ferrone M, Slater JB, Xu D, Kurhanewicz J, Vigneron DB, Chang S, Nelson SJ. Development of methods and feasibility of using hyperpolarized carbon-13 imaging data for evaluating brain metabolism in patient studies. Magn Reson Med. 2018 Sep;80(3):864-873. doi: 10.1002/mrm.27077. Epub 2018 Jan 10.
• Background Gordon JW, Chen HY, Nickles T, Lee PM, Bok R, Ohliger MA, Okamoto K, Ko AH, Larson PEZ, Wang ZJ. Hyperpolarized 13C Metabolic MRI of Patients with Pancreatic Ductal Adenocarcinoma. J Magn Reson Imaging. 2024 Aug;60(2):741-749. doi: 10.1002/jmri.29162. Epub 2023 Dec 2.

Drugs

Indications