title: Detection of inflammatory cell function using (13)C magnetic resonance spectroscopy of hyperpolarized [6-(13)C]-arginine.
abstract: Myeloid-derived suppressor cells (MDSCs) are highly prevalent inflammatory cells that play a key role in tumor development and are considered therapeutic targets. MDSCs promote tumor growth by blocking T-cell-mediated anti-tumoral immune response through depletion of arginine that is essential for T-cell proliferation. To deplete arginine, MDSCs express high levels of arginase, which catalyzes the breakdown of arginine into urea and ornithine. Here, we developed a new hyperpolarized (13)C probe, [6-(13)C]-arginine, to image arginase activity. We show that [6-(13)C]-arginine can be hyperpolarized, and hyperpolarized [(13)C]-urea production from [6-(13)C]-arginine is linearly correlated with arginase concentration in vitro. Furthermore we show that we can detect a statistically significant increase in hyperpolarized [(13)C]-urea production in MDSCs when compared to control bone marrow cells. This increase was associated with an increase in intracellular arginase concentration detected using a spectrophotometric assay. Hyperpolarized [6-(13)C]-arginine could therefore serve to image tumoral MDSC function and more broadly M2-like macrophages.
authors: Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA.
authors: Chloé
authors: C
authors: Najac
authors: Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA.
authors: Myriam M
authors: MM
authors: Chaumeil
authors: Department of Neurological Surgery, University of Surgery, University of California San Francisco, San Francisco, CA, USA.
authors: Gary
authors: G
authors: Kohanbash
authors: Bio-imaging Lab, University of Antwerp, Antwerpen, Belgium.
authors: Caroline
authors: C
authors: Guglielmetti
authors: Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA.
authors: Jeremy W
authors: JW
authors: Gordon
authors: Department of Neurological Surgery, University of Surgery, University of California San Francisco, San Francisco, CA, USA.
authors: Hideho
authors: H
authors: Okada
authors: Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA.
authors: Sabrina M
authors: SM
authors: Ronen
mesh_terms: D000818:Animals; D001119:Arginase / Q000378:metabolism*; D001120:Arginine / Q000737:chemistry / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D002478:Cells, Cultured; D051379:Mice; D000072737:Myeloid-Derived Suppressor Cells / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism; D014508:Urea / Q000737:chemistry
chemical_list: D014508:Urea; D001120:Arginine; D001119:Arginase