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COMPARISON OF MEASUREMENTS OF CEREBRAL BLOOD FLOW BY EARLY FRAMES OF 11C-DEUTERIUM-L-DEPRENYL (11C-DED) AND 11C-PIB PET TRACERS AT DIFFERENT STAGES OF ALZHEIMER'S DISEASE

      Background: The pathophysiological mechanisms of Alzheimer's disease (AD) are complex and there is evidence that neuroinflammatory and neurovascular changes may precede β -amyloid (A β) plaque deposition in AD. Reactive astrocytes seem to play an important role in neuroprotective or neurotoxic mechanisms at different stages of AD, and are also involved in neurovascular dysfunction. The PET tracer 11 C-deuterium-L-deprenyl (11 C-DED), which binds to monoamine oxidase B (MAO-B) and a marker of astrocytosis, was applied together with 11 C-PIB and 18 F-FDG in a multi-tracer study. Here we wanted to compare 11 C-DED and 11 C-PIB early frames as measures of cerebral blood flow (CBF) at different stages of Alzheimer's disease.
      Methods: 11 C-DED, 11 C-PIB and 18 F-FDG PET scans were performed in 64 subjects including sporadic AD (n=8), sporadic MCI with or without fibrillar A β deposition (n=16), healthy controls (n=14), and members of families with known AD mutations (n=26). Mean target-to-pons regional values were obtained for 11 C-PIB and 18 F-FDG, while a modified reference (cerebellum gray matter) Patlak model was applied to 11 C-DED.
      Results: In this study, the 1-4 minute early frames of 11 C-DED (eDED) and 11 C-PIB (ePIB) were compared as estimates of CBF at different stages of AD as well as in controls. CBF as measured by eDED was found to be significantly decreased in MCI PIB-positive patients compared to healthy controls in most cortical regions and in the putamen. In contrast, no significant CBF changes were detected in presymptomatic familial AD (FAD) mutation carriers when compared to age-matched non-carriers. However, CBF in presymptomatic FAD carriers declined in time when approaching estimated age of onset. CBF changes as measured by ePIB were compared to the estimates using eDED as well as the 18 F-FDG uptake in the same study groups.
      Conclusions: The use of early frames of 11 C-DED and 11 C-PIB tracers as measures of CBF in addition to binding data in the late frames offers the advantage of obtaining dual physiological (CBF) and pathological information from a single PET scan. The measurement of CBF from these tracers contributes to the understanding of the time course and regional brain changes at different stages in AD.