Imst-04. Imaging Inflammatory Cell Function Using 13c Magnetic Resonance Spectroscopy of Hyperpolarized 6-13c-labeled Arginine
Year: 2016
Type: conference-abstract
Abstract: Inflammation is now recognized as an important hallmark of cancer, and immunotherapies offer a promising therapeutic approach. In particular, myeloid-derived suppressor cells (MDSCs) are highly prevalent inflammatory cells that play a key role in tumor development and are considered as potential therapeutic targets in the treatment of glioblastoma. 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, the enzyme that catalyzes the breakdown of arginine into urea and ornithine. However, currently, there are no non-invasive imaging methods that can monitor MDSC function or arginase activity, limiting our ability to assess the efficacy of MDSC-targeting immunotherapies. Hyperpolarized 13C magnetic resonance spectroscopy (MRS) is a novel non-invasive imaging method that can monitor metabolism within seconds. The objective of this study was to use this new method and image arginase activity by monitoring the fate of hyperpolarized 6-13C-labeled arginine, a previously unexplored imaging probe. First we demonstrated that 6-13C-labeled arginine can be hyperpolarized, and that its MRS-detectable metabolism to urea is linearly correlated with arginase concentration in vitro. Then we investigated cells. Bone marrow (BM) cells isolated from Balb/c mice were cultured with cytokines. At day 4 cells were separated into two groups: control BM cells and MDSCs, generated by treating BM cells with interleukin-13. Up-regulation of arginase concentration in MDSCs was confirmed using a spectrophotometric assay. Then, we demonstrated that we were able to detect a statistically significant increase in the production of hyperpolarized 13C-labeled urea in MDSCs when compared to control BM cells. This confirmed the utility of hyperpolarized 13C MRS with 6-13C-labeled arginine as an imaging approach for monitoring arginase expression in cells. This method could be used to image tumoral MDSC function and its inhibition following MDSC-targeted immunotherapies.
Source: Neuro-Oncology
Language: English
Subfield: Spectroscopy
Field: Chemistry
Domain: Physical Sciences
Open Access status: bronze
OpenAlex ID: W2588883666