Detection of inflammatory cell function using $^{13}C$ magnetic resonance spectroscopy of hyperpolarized [6-$^{13}C$]-arginine

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 C-13 probe, [6-C-13]-arginine, to image arginase activity. We show that [6-C-13]-arginine can be hyperpolarized, and hyperpolarized [C-13]-urea production from [6-C-13-arginine is linearly correlated with arginase concentration in vitro. Furthermore we show that we can detect a statistically significant increase in hyperpolarized [C-13]-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-C-13-arginine could therefore serve to image tumoral MDSC function and more broadly M2-like macrophages.

Publication year:2016

Keywords:A1 Journal article

BOF-keylabel:yes

BOF-publication weight:6

CSS-citation score:1

Authors:International

Authors from:Higher Education

Accessibility:Open