Alzheimer's disease (AD) is defined histologically by the presence of extracellular β-amyloid (Aβ) plaques and intraneuronal neurofibrillary tangles in the cerebral cortex. The diagnosis of dementia, along with the prediction of who will develop dementia, has been assisted by magnetic resonance imaging and positron emission tomography (PET) by using ( 18 F)fluorodeoxyglucose (FDG). These techniques, however, are not specific for AD. Based on the chemistry of histologic staining dyes, several Aβ-specific positron-emitting radiotracers have been developed to image neuropathology of AD. Among these, ( 11 C)PiB is the most studied Aβ-binding PET radiopharmaceutical in the world. The histologic and biochemical specificity of PiB binding across different regions of the AD brain was demonstrated by showing a direct correlation between Aβ-containing amyloid plaques and in vivo ( 11 C)PiB retention measured by PET imaging. Because 11 C is not ideal for commercialization, several 18 F-labeled tracers have been developed. At this time, ( 18 F)3′-F-PiB (Flutemetamol), 18 F-AV-45 (Florbetapir), and 18 F-AV-1 (Florbetaben) are undergoing extensive phase II and III clinical trials. This article provides a brief review of the amyloid biology and chemistry of Aβ-specific 11 C and 18 F-PET radiopharmaceuticals. Clinical trials have clearly documented that PET radiopharmaceuticals capable of assessing Aβ content in vivo in the brains of AD subjects and subjects with mild cognitive impairment will be important as diagnostic agents to detect in vivo amyloid brain pathology. In addition, PET amyloid imaging will also help test the amyloid cascade hypothesis of AD and as an aid to assess the efficacy of antiamyloid therapeutics currently under development in clinical trials.
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Positron Emission Tomography Radiopharmaceuticals for Imaging Brain Beta-Amyloid
Vallabhajosula, Shankar
Follow Seminars in Nuclear Medicine
, Volume 41 (4)
Elsevier – Jul 1, 2011
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