The new research diagnostic criteria for AD and MCI allow for A?? imaging in the workup of individuals selleck bio with cognitive impairment [5,6]. Non-invasive A?? imaging to confirm the presence of AD neuropathology could aid in early differential diagnosis, identify at-risk individuals, help predict or monitor disease progression, and potentially evaluate the response to disease-specific therapy. 11C-Pittsburgh Compound B (PiB) has been the most widely used agent in dementia research to assess A?? burden in vivo [7]. The major disadvantage of PiB is that it is radiolabeled with carbon-11, which has a short decay half-life (20 minutes) that limits its use to centers with an onsite cyclotron and 11C-radiochemistry expertise.
To overcome these limitations, a number of novel fluorine-18 A?? imaging tracers such as 18F-florbetaben (BAY 94-9172) [8-10], 18F-florbetapir (AV45) [11,12] and 18F-flutemetamol (GE067) [13,14] have been developed. The 110-minute radioactive decay half-life of fluorine-18 allows centralized synthesis and regional distribution of these tracers as currently practiced worldwide in the supply of 18F-fluorodeoxyglucose for routine clinical positron emission tomography (PET) imaging. 18F-florbetaben (FBB; trans-4-(N-methyl-amino)-4″(2-(2-(2-[18F] fluoro-ethoxy)ethoxy)-ethoxy)stilbene), developed by Avid Radiopharmaceuticals (Philadelphia, USA) and Bayer-Schering Pharma (Berlin, Germany), has been shown to bind with high affinity to A?? in brain homogenates and selectively labeled A?? plaques and cerebral amyloid angiopathy (CAA) in AD tissue sections [15].
After injection into Tg2576 transgenic mice, ex vivo brain sections showed localization of FBB in regions with A?? plaques as confirmed by thioflavin binding [16]. At the tracer concentrations achieved during human PET studies, FBB did not show binding to ??-synuclein in Lewy bodies or to tau lesions in postmortem cortices from dementia with Lewy bodies, AD or frontotemporal lobar degeneration patients [17]. In human studies, cortical retention of FBB was significantly higher in AD patients compared with age-matched controls and frontotemporal lobar degeneration patients, with binding matching the reported postmortem distribution of A?? plaques [9]. Phase II clinical studies further confirmed these results [8]. FBB is highly correlated with 11C-PiB (r = 0.97 GSK-3 with a slope of 0.
71) [18], free copy and was used to detect the presence or absence of AD pathology in the brain in participants with a wide spectrum of neurodegenerative diseases including a few MCI participants [10]. Phase III studies for FBB have reached completion [19]. Human postmortem studies have shown that while soluble A?? oligomers and the density of neurofibrillary tangles strongly correlate with neurodegeneration and cognitive deficits, the density of A?? insoluble plaques does not [20-24] and ???? burden as assessed by PET does not strongly correlate with cognitive impairment in AD patients [25,26].