More than a decade ago, Klunk and colleagues1 published the first study applying the positron emission tomography (PET) ligand carbon 11–labeled Pittsburgh Compound B to image amyloid-β (Aβ) plaques in patients with Alzheimer disease (AD). In subsequent years, amyloid PET has had a transformative impact on AD research, leading to refined models of disease pathogenesis, providing in vivo evidence for a prolonged preclinical disease phase, and ultimately setting the stage for therapeutic trials aimed at delaying or even preventing the symptomatic phase of AD.2,3 Beyond research applications, amyloid PET has great potential as a diagnostic tool. The clinical diagnosis of AD, even in the hands of experts, has only moderate sensitivity and specificity when compared with the pathological cause of dementia as determined at autopsy.4 Misdiagnosis rates approaching 30% have implications for patient care and may be a major confounder in AD clinical trials.5 Amyloid PET has the potential to improve diagnostic accuracy by directly detecting a core element of AD pathology. While carbon 11–labeled Pittsburgh Compound B has limited prospects as a clinical diagnostic given the short half-life of the carbon 11 radioisotope (20 minutes), a number of Aβ PET tracers radiolabelled with fluorine 18 (18F), a longer-lived isotope (half-life = 110 minutes) used extensively in nuclear medicine, have been developed for clinical applications.6 These include [18F]flutemetamol, an 18F-labeled derivative of Pittsburgh Compound B that performed comparably with the parent compound in initial clinical studies.7
Rabinovici GD. The Translational Journey of Brain β-Amyloid Imaging: From Positron Emission Tomography to Autopsy to Clinic. JAMA Neurol. 2015;72(3):265–266. doi:10.1001/jamaneurol.2014.4143
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