Figure 1.
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.