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Objective: Currently [18F]FDDNP is the only PET imaging probe with the ability to visualize hyperphosphorylated tau fibrillar aggregates in living subjects. In this work, we evaluate in vivo [18F]FDDNP labeling of brain neuropathology, primarily tau fibrillar aggregates, in patients with progressive supranuclear palsy (PSP), a human tauopathy usually lacking amyloid-β deposits., Methods: Fifteen patients with PSP received [18F]FDDNP PET scanning. [18F]FDDNP distribution volume ratios, in reference to cerebellar gray matter, were determined for cortical and subcortical areas and compared with those of patients with Parkinson's disease with short disease duration, and age-matched control subjects without neurodegenerative disorders., Results: [18F]FDDNP binding was present in subcortical areas (e.g., striatum, thalamus, subthalamic region, midbrain, and cerebellar white matter) regardless of disease severity, with progressive subcortical and cortical involvement as disease severity increased. Brain patterns of [18F]FDDNP binding were entirely consistent with the known pathology distribution for PSP. High midbrain and subthalamic region [18F]FDDNP binding was distinctive for PSP subjects and separated them from controls and patients with Parkinson's disease., Conclusions: These results provide evidence that [18F]FDDNP is a sensitive in vivo PET imaging probe to map and quantify the dynamic regional localization of tau fibrillar aggregates in PSP. Furthermore, [18F]FDDNP PET may provide a tool to detect changes in tau pathology distribution either associated with disease progression or as a treatment biomarker for future tau-specific therapies. Patterns of [18F]FDDNP binding may also be useful in diagnosis early in disease presentation when clinical distinction among neurodegenerative disorders is often difficult.

Adult male volunteers were exposed to nitrogen dioxide (NO2) at 1.0 ppm in purified air under conditions simulating ambient photochemical smog exposures (2-hr exposure with intermittent light exercise at 31 degrees C and 35% relative humidity). Sham exposures to purified air alone served as controls. Exposure effects were assessed by pulmonary physiological tests and by a standardized clinical evaluation. No statistically physiological changes attributable to NO2 exposure were found except for a marginal loss in forced vital capacity after exposure on two successive days (1.5% mean decrease, P less than .05). Reported respiratory and other symptoms were slightly increased with exposure as compared to control, but the change was not significant. Short-term toxicity of NO2 at peak ambient concentrations appears to be substantially less than that of ozone in healthy people, but adverse NO2 effects in diseased people or in long-term exposures cannot be ruled out at present.