Reduced microglia activity in patients with long-term immunosuppressive therapy after liver transplantation.

PURPOSE: Calcineurin inhibitors (CNI) can cause long-term impairment of brain function. Possible pathomechanisms include alterations of the cerebral immune system. This study used positron emission tomography (PET) imaging with the translocator protein (TSPO) ligand 18F-GE-180 to evaluate microglial activation in liver-transplanted patients under different regimens of immunosuppression. METHODS: PET was performed in 22 liver-transplanted patients (3 CNI free, 9 with low-dose CNI, 10 with standard-dose CNI immunosuppression) and 9 healthy controls. The total distribution volume (VT) estimated in 12 volumes-of-interest was analyzed regarding TSPO genotype, CNI therapy, and cognitive performance. RESULTS: In controls, VT was about 80% higher in high affinity binders (n = 5) compared to mixed affinity binders (n = 3). Mean VT corrected for TSPO genotype was significantly lower in patients compared to controls, especially in patients in whom CNI dose had been reduced because of nephrotoxic side effect. CONCLUSION: Our results provide evidence of chronic suppression of microglial activity in liver-transplanted patients under CNI therapy especially in patients with high sensitivity to CNI toxicity.

Reliable quantification of 18F-GE-180 PET neuroinflammation studies using an individually scaled population-based input function or late tissue-to-blood ratio.

PURPOSE: Tracer kinetic modeling of tissue time activity curves and the individual input function based on arterial blood sampling and metabolite correction is the gold standard for quantitative characterization of microglia activation by PET with the translocator protein (TSPO) ligand 18F-GE-180. This study tested simplified methods for quantification of 18F-GE-180 PET. METHODS: Dynamic 18F-GE-180 PET with arterial blood sampling and metabolite correction was performed in five healthy volunteers and 20 liver-transplanted patients. Population-based input function templates were generated by averaging individual input functions normalized to the total area under the input function using a leave-one-out approach. Individual population-based input functions were obtained by scaling the input function template with the individual parent activity concentration of 18F-GE-180 in arterial plasma in a blood sample drawn at 27.5 min or by the individual administered tracer activity, respectively. The total 18F-GE-180 distribution volume (VT) was estimated in 12 regions-of-interest (ROIs) by the invasive Logan plot using the measured or the population-based input functions. Late ROI-to-whole-blood and ROI-to-cerebellum ratio were also computed. RESULTS: Correlation with the reference VT (with individually measured input function) was very high for VT with the population-based input function scaled with the blood sample and for the ROI-to-whole-blood ratio (Pearson correlation coefficient = 0.989 ± 0.006 and 0.970 ± 0.005). The correlation was only moderate for VT with the population-based input function scaled with tracer activity dose and for the ROI-to-cerebellum ratio (0.653 ± 0.074 and 0.384 ± 0.177). Reference VT, population-based VT with scaling by the blood sample, and ROI-to-whole-blood ratio were sensitive to the TSPO gene polymorphism. Population-based VT with scaling to the administered tracer activity and the ROI-to-cerebellum ratio failed to detect a polymorphism effect. CONCLUSION: These results support the use of a population-based input function scaled with a single blood sample or the ROI-to-whole-blood ratio at a late time point for simplified quantitative analysis of 18F-GE-180 PET.

New horizons in microparticle forensics: Actinide imaging and detection of 238Pu and 242mAm in hot particles.

Micrometer-sized pollutant particles are of highest concern in environmental and life sciences, cosmochemistry, and forensics. From their composition, detailed information on origin and potential risks to human health or environment is obtained. We combine secondary ion mass spectrometry with resonant laser ionization to selectively examine elemental and isotopic composition of individual particles at submicrometer spatial resolution. Avoiding any chemical sample preparation, isobaric interferences are suppressed by five orders of magnitude. In contrast to most mass spectrometric techniques, only negligible mass is consumed, leaving the particle intact for further studies. Identification of actinide elements and their isotopes on a Chernobyl hot particle, including 242mAm at ultratrace levels, proved the performance. Beyond that, the technique is applicable to almost all elements and opens up previously unexplored scientific applications.

Investigation of low-level 242Pu contamination on nutrition disturbance and oxidative stress in Solanum tuberosum L.

Plutonium associated with higher molecular weight molecules is presumed to be poorly mobile and hardly plant available. In our present study, we investigate the uptake and effects of Pu treatments on Solanum tuberosum plants in amended Hoagland medium at concentrations of [242Pu] = 100 and 500 nm, respectively. We found a direct proof of oxidative stress in the plants caused by these rather low concentrations. For the confirmation of oxidative stress, we explored the production of nitric oxide (NO) and hydrogen peroxide (H2O2) by epifluorescence microscopy. Oxidative stress markers like lipid peroxidation and superoxide radicals (O2•-) are monitored through histochemical analysis. The biochemical parameters i.e. chlorophyll and carotenoids are measured as an indicator of cellular damage in the tested plants including the enzymatic parameters such as catalase and glutathione reductase. From our work, we conclude that Pu in low concentration has no significant effects on the uptake of many trace and macroelements. In contrast, the content of O2•- , malondialdehyde (MDA), and H2O2 increases with increasing Pu concentration in the solution, while the opposite effects was found for NO, catalase, and glutathione reductase. These findings prove that even low concentration of Pu regulates ROS production and generate oxidative stress in S. tuberosum L.