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. 2018 May 21;8:7928. doi: 10.1038/s41598-018-26296-6

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© The Author(s) 2018

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Ascorbates as redox imaging probes. (a) Dehydroascorbate (DHA) can traverse the blood-brain-barrier, enter cells via glucose transporter (GLUT)1,3,4 and be rapidly reduced to ascorbic acid (vitamin C, VitC) by intracellular antioxidants including glutathione (GSH), which is coupled with the pentose phosphate pathway via NADPH. The conversion from hyperpolarized [1-¹³C]DHA to [1-¹³C]VitC can be monitored by MR spectroscopy, taking advantage of their unique chemical shifts. The C1 position of DHA and VitC can also be labelled with ¹¹C for PET and biodistribution studies. (b) In these PET images (adapted from Carroll et al.²¹), the accumulation of [1-¹¹C]DHA in the normal rat brain is compared to that of [1-¹¹C]VitC in the normal rat brain. In normal rats, higher brain signal for [1-¹¹C]DHA is expected since it readily crosses the blood-brain barrier and is transported into cells via GLUT transporters. In contrast, transport of VitC into the brain via sodium-dependent vitamin C transporter-2 (SVCT2) is a slower process. Unlike measuring the real-time conversion rate by hyperpolarized MR, PET and biodistribution with [¹¹C]ascorbates measures the uptake and retention of ¹¹C radiopharmaceuticals.