Fluorine labelling of therapeutic human tolerogenic dendritic cells for 19F-magnetic resonance imaging.

Tolerogenic dendritic cell (tolDC) therapies aim to restore self-tolerance in patients suffering from autoimmune diseases. Phase 1 clinical trials with tolDC have shown the feasibility and safety of this approach, but have also highlighted a lack of understanding of their distribution in vivo. Fluorine-19 magnetic resonance imaging (19F-MRI) promises an attractive cell tracking method because it allows for detection of 19F-labelled cells in a non-invasive and longitudinal manner. Here, we tested the suitability of nanoparticles containing 19F (19F-NP) for labelling of therapeutic human tolDC for detection by 19F-MRI. We found that tolDC readily endocytosed 19F-NP with acceptable effects on cell viability and yield. The MRI signal-to-noise ratios obtained are more than sufficient for detection of the administered tolDC dose (10 million cells) at the injection site in vivo, depending on the tissue depth and the rate of cell dispersal. Importantly, 19F-NP labelling did not revert tolDC into immunogenic DC, as confirmed by their low expression of typical mature DC surface markers (CD83, CD86), low secretion of pro-inflammatory IL-12p70, and low capacity to induce IFN-γ in allogeneic CD4+ T cells. In addition, the capacity of tolDC to secrete anti-inflammatory IL-10 was not diminished by 19F-NP labelling. We conclude that 19F-NP is a suitable imaging agent for tolDC. With currently available technologies, this imaging approach does not yet approach the sensitivity required to detect small numbers of migrating cells, but could have important utility for determining the accuracy of injecting tolDC into the desired target tissue and their efflux rate.

Sucrose ingestion after exhaustive exercise accelerates liver, but not muscle glycogen repletion compared with glucose ingestion in trained athletes.

The purpose of this study was to assess the effects of sucrose vs. glucose ingestion on postexercise liver and muscle glycogen repletion. Fifteen well-trained male cyclists completed two test days. Each test day started with glycogen-depleting exercise, followed by 5 h of recovery, during which subjects ingested 1.5 g·kg(-1)·h(-1) sucrose or glucose. Blood was sampled frequently and (13)C magnetic resonance spectroscopy and imaging were employed 0, 120, and 300 min postexercise to determine liver and muscle glycogen concentrations and liver volume. Results were as follows: Postexercise muscle glycogen concentrations increased significantly from 85 ± 27 (SD) vs. 86 ± 35 mmol/l to 140 ± 23 vs. 136 ± 26 mmol/l following sucrose and glucose ingestion, respectively (no differences between treatments: P = 0.673). Postexercise liver glycogen concentrations increased significantly from 183 ± 47 vs. 167 ± 65 mmol/l to 280 ± 72 vs. 234 ± 81 mmol/l following sucrose and glucose ingestion, respectively (time × treatment, P = 0.051). Liver volume increased significantly over the 300-min period after sucrose ingestion only (time × treatment, P = 0.001). As a result, total liver glycogen content increased during postexercise recovery to a greater extent in the sucrose treatment (from 53.6 ± 16.2 to 86.8 ± 29.0 g) compared with the glucose treatment (49.3 ± 25.5 to 65.7 ± 27.1 g; time × treatment, P < 0.001), equating to a 3.4 g/h (95% confidence interval: 1.6-5.1 g/h) greater repletion rate with sucrose vs. glucose ingestion. In conclusion, sucrose ingestion (1.5 g·kg(-1)·h(-1)) further accelerates postexercise liver, but not muscle glycogen repletion compared with glucose ingestion in trained athletes.

Ingestion of glucose or sucrose prevents liver but not muscle glycogen depletion during prolonged endurance-type exercise in trained cyclists.

The purpose of this study was to define the effect of glucose ingestion compared with sucrose ingestion on liver and muscle glycogen depletion during prolonged endurance-type exercise. Fourteen cyclists completed two 3-h bouts of cycling at 50% of peak power output while ingesting either glucose or sucrose at a rate of 1.7 g/min (102 g/h). Four cyclists performed an additional third test for reference in which only water was consumed. We employed (13)C magnetic resonance spectroscopy to determine liver and muscle glycogen concentrations before and after exercise. Expired breath was sampled during exercise to estimate whole body substrate use. After glucose and sucrose ingestion, liver glycogen levels did not show a significant decline after exercise (from 325 ± 168 to 345 ± 205 and 321 ± 177 to 348 ± 170 mmol/l, respectively; P > 0.05), with no differences between treatments. Muscle glycogen concentrations declined (from 101 ± 49 to 60 ± 34 and 114 ± 48 to 67 ± 34 mmol/l, respectively; P < 0.05), with no differences between treatments. Whole body carbohydrate utilization was greater with sucrose (2.03 ± 0.43 g/min) vs. glucose (1.66 ± 0.36 g/min; P < 0.05) ingestion. Both liver (from 454 ± 33 to 283 ± 82 mmol/l; P < 0.05) and muscle (from 111 ± 46 to 67 ± 31 mmol/l; P < 0.01) glycogen concentrations declined during exercise when only water was ingested. Both glucose and sucrose ingestion prevent liver glycogen depletion during prolonged endurance-type exercise. Sucrose ingestion does not preserve liver glycogen concentrations more than glucose ingestion. However, sucrose ingestion does increase whole body carbohydrate utilization compared with glucose ingestion. This trial was registered at https://www.clinicaltrials.gov as NCT02110836.