Because a correlation between tau pathology and the clinical symptoms of Alzheimer disease (AD) has been hypothesized, there is increasing interest in developing PET tracers that bind specifically to tau protein. The aim of this study was to evaluate tracer kinetic models for quantitative analysis and generation of parametric images for the novel tau ligand (S)-18 F-THK5117. Methods: Nine subjects (5 with AD, 4 with mild cognitive impairment) received a 90-min dynamic (S)-18 F-THK5117 PET scan. Arterial blood was sampled for measurement of blood radioactivity and metabolite analysis. Volume-ofinterest (VOI)-based analysis was performed using plasma-input models; single-tissue and 2-tissue (2TCM) compartment models and plasma-input Logan and reference tissue models; and simplified reference tissue model (SRTM), reference Logan, and SUV ratio (SUVr). Cerebellum gray matter was used as the reference region. Voxel-level analysis was performed using basis function implementations of SRTM, reference Logan, and SUVr. Regionally averaged voxel values were compared with VOI-based values from the optimal reference tissue model, and simulations were made to assess accuracy and precision. In addition to 90 min, initial 40-and 60-min data were analyzed. Results: Plasma-input Logan distribution volume ratio (DVR)-1 values agreed well with 2TCM DVR-1 values (R 2 5 0.99, slope 5 0.96). SRTM binding potential (BP ND ) and reference Logan DVR-1 values were highly correlated with plasma-input Logan DVR-1 (R 2 5 1.00, slope ≈ 1.00) whereas SUVr 70-90 -1 values correlated less well and overestimated binding. Agreement between parametric methods and SRTM was best for reference Logan (R 2 5 0.99, slope 5 1.03). SUVr 70-90 -1 values were almost 3 times higher than BP ND values in white matter and 1.5 times higher in gray matter. Simulations showed poorer accuracy and precision for SUVr 70-90 -1 values than for the other reference methods. SRTM BP ND and reference Logan DVR-1 values were not affected by a shorter scan duration of 60 min. Conclusion: SRTM BP ND and reference Logan DVR-1 values were highly correlated with plasma-input Logan DVR-1 values. VOI-based data analyses indicated robust results for scan durations of 60 min. Reference Logan generated quantitative (S)-18 F-THK5117 DVR-1 parametric images with the greatest accuracy and precision and with a much lower white-matter signal than seen with SUVr 70-90 -1 images.

Smoking is a cause of serious disease in smokers. Electronic cigarettes, delivering aerosolized nicotine, offer adult smokers a potentially less harmful alternative to combustible cigarettes. This explorative PET/CT study investigated the distribution and deposition of inhaled [11C]nicotine using the mybluTM e-cigarette with two nicotine formulations, freebase and lactate salt. Fifteen healthy adult smokers participated in the two-part study to assess the distribution and accumulation of [11C]nicotine in the respiratory pathways and brain. Time-activity data for the respiratory pathways, lungs, oesophagus and brain were derived. 31–36% of both inhaled tracer formulations accumulated in the lung within 15–35 s. [11C]Nicotinefreebase exhibited higher uptake and deposition in the upper respiratory pathways. For [11C]nicotinelactate, brain deposition peaked at 4–5%, with an earlier peak and a steeper decline. A different kinetic profile was obtained for [11C]nicotinelactate with lower tracer uptake and accumulation in the upper respiratory pathways and an earlier peak and a steeper decline in lung and brain. Using nicotine lactate formulations in e-cigarettes may thus contribute to greater adult smoker acceptance and satisfaction compared to freebase formulations, potentially aiding a transition from combustible cigarettes and an acceleration of tobacco harm reduction initiatives.

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A transient increase in intracellular free calcium is believed to be the signal responsible for the stimulation of the egg metabolism at fertilization and the resumption of the cell cycle. We have studied how the polyphosphoinositides (PPI) turn over at fertilization in sea urchin eggs, in order to determine the relationship between the metabolism of these lipids and the calcium signal. We compare the patterns of PPI turnover that occur during the first minute following fertilization in eggs in which PPI are labelled to steady state with [3H]inositol or [3H]arachidonate with that in which PPI are labelled for a shorter period with [3H]inositol. When eggs are labelled to apparent isotopic equilibrium with either [3H]inositol or [3H]arachidonate, no early increase in [3H]PtdInsP2 occurs while PtdIns decreases slightly. On the contrary, when not labelled to isotopic equilibrium, all [3H]PPI increase during the first 15 seconds following fertilization. We find that, within seconds, fertilization triggers a 600-fold increase in the turnover of PPI, producing an amount of InsP3 apparently sufficient to trigger calcium release. We suggest that phosphoinositidase C and PtdInsP kinase, responsible respectively for the hydrolysis and synthesis of PtdInsP2, are both stimulated to a comparable degree in the first 30 seconds following fertilization and that net changes in the amount of PtdInsP2 at fertilization are very sensitive to the relative levels of activation of the two enzymes. Activating the eggs with the calcium ionophore A23187 showed that both these enzymes are sensitive to calcium, suggesting that calcium-dependent InsP3 production might play a role in the initiation and/or the propagation of the fertilization calcium wave.(ABSTRACT TRUNCATED AT 250 WORDS)