ArticleCancer research2014
Monitoring chemotherapeutic response by hyperpolarized 13C-fumarate MRS and diffusion MRI.
Article in Cancer research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 55 citations in OpenAlex.
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- Parahydrogen-induced polarization allows 2000-fold signal enhancement in biologically active derivatives of the peptide-based drug octreotide.Scientific reports · 2023Article
- Application and development of Deuterium Metabolic Imaging in tumor glucose metabolism: visualization of different metabolic pathways.Frontiers in oncology · 2023Review
- Deuterium MRSI of tumor cell death in vivo following oral delivery ofMagnetic resonance in medicine · 2022Article
- Recent advances in the application of parahydrogen in catalysis and biochemistry.RSC advances · 2022Review
- In vivo Human MR Spectroscopy Using a Clinical Scanner: Development, Applications, and Future Prospects.Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine · 2022Review
- Direct Production of a Hyperpolarized Metabolite on a Microfluidic Chip.Analytical chemistry · 2022Article
- Article
- Multimodal Molecular Imaging Detects Early Responses to Immune Checkpoint Blockade.Cancer research · 2021Article
- Rapid hyperpolarization and purification of the metabolite fumarate in aqueous solution.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Monitoring tumor cell death in murine tumor models using deuterium magnetic resonance spectroscopy and spectroscopic imaging.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Singlet-Contrast Magnetic Resonance Imaging: Unlocking Hyperpolarization with Metabolism*.Angewandte Chemie (International ed. in English) · 2021Article
- HyperpolarizedRadiology · 2019Review
- MARCH1 encourages tumour progression of hepatocellular carcinoma via regulation of PI3K-AKT-β-catenin pathways.Journal of cellular and molecular medicine · 2019Article
- Assessing Therapeutic Efficacy in Real-time by Hyperpolarized Magnetic Resonance Metabolic Imaging.Cells · 2019Review
- Secalonic Acid-F, a Novel Mycotoxin, Represses the Progression of Hepatocellular Carcinoma via MARCH1 Regulation of the PI3K/AKT/β-catenin Signaling Pathway.Molecules (Basel, Switzerland) · 2019Article
- HyperpolarizedNeoplasia (New York, N.Y.) · 2019Review
- Development of methods and feasibility of using hyperpolarized carbon-13 imaging data for evaluating brain metabolism in patient studies.Magnetic resonance in medicine · 2018Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Targeted chemotherapeutic agents often do not result in tumor shrinkage, so new biomarkers that correlate with clinical efficacy are needed. In this study, we investigated noninvasive imaging protocols to monitor responses to sorafenib, a multikinase inhibitor approved for treatment of renal cell and hepatocellular carcinoma. Healthy cells are impermeable to fumarate, so conversion of this metabolite to malate as detected by (13)C-magnetic resonance spectroscopy (MRS) has been suggested as one marker for cell death and treatment response in tumors. Diffusion MRI also has been suggested as a measure of therapy-induced cytotoxic edema because viable cells act as a diffusion barrier in tissue. For these reasons, we assessed sorafenib responses using hyperpolarized (13)C-fumarate, diffusion-weighted MRI (DW-MRI) in a xenograft model of human breast cancer in which daily administration of sorafenib was sufficient to stabilize tumor growth. We detected signals from fumarate and malate following intravenous administration of hyperpolarized fumarate with a progressive increase in the malate-to-fumarate (MA/FA) ratio at days 2 to 5 after sorafenib infusion. The apparent diffusion coefficient (ADC) measured by DW-MRI increased in the treated group consistent with cytotoxic edema. However, the MA/FA ratio was a more sensitive marker of therapeutic response than ADC, with 2.8-fold versus 1.3-fold changes, respectively, by day 5 of drug treatment. Histologic analyses confirmed cell death in the sorafenib-treated cohort. Notably, (13)C-pyruvate-to-lactate conversion was not affected by sorafenib in the breast cancer model examined. Our results illustrate how combining hyperpolarized substrates with DW-MRI can allow noninvasive monitoring of targeted therapeutic responses at relatively early times after drug administration.
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