Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA.
Department of Neurological Surgery, University of Surgery, University of California San Francisco, San Francisco, CA, USA.
Sci Rep. 2016 Aug 10;6:31397. doi: 10.1038/srep31397.
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.
髓系来源的抑制细胞（MDSCs）是高度普遍存在的炎症细胞，在肿瘤发展中发挥关键作用，并被认为是治疗靶点。MDSCs 通过消耗精氨酸来阻止 T 细胞介导的抗肿瘤免疫反应，从而促进肿瘤生长，精氨酸是 T 细胞增殖所必需的。为了消耗精氨酸，MDSCs 表达高水平的精氨酸酶，该酶将精氨酸分解成尿素和鸟氨酸。在这里，我们开发了一种新的超极化（13）C 探针 [6-（13）C]-精氨酸，用于成像精氨酸酶活性。我们表明 [6-（13）C]-精氨酸可以被超极化，并且 [6-（13）C]-精氨酸转化为 [13C]-尿素的产量与体外精氨酸酶浓度呈线性相关。此外，我们表明，与对照骨髓细胞相比，我们可以检测到 MDSC 中超极化 [13C]-尿素产量的统计学显著增加。这种增加与使用分光光度法检测到的细胞内精氨酸酶浓度的增加有关。因此，超极化 [6-（13）C]-精氨酸可用于成像肿瘤 MDSC 功能，更广泛地用于 M2 样巨噬细胞。
