Amyloid Imaging in Alzheimer’s Disease
Multiple PET radiotracers have been developed to image amyloid-β (Aβ) plaques in the brain, to assist in the diagnosis of Alzheimer’s disease. PET imaging may show abnormal radiotracer uptake before morphologic abnormalities are evident on MRI.
Most early research into PET imaging of Aβ has been performed with C11 Pittsburgh compound B (PIB). However clinical application with this tracer is limited by the 20 minute half-life, necessitating an on-site cylcotron.
Several PET tracers using Fluorine-18 have been recently FDA approved for this indication, including florbetapir, flutemetamol, and florbetaben. This enables more widespread use of amyloid imaging in the evaluation of patients with cognitive impairment and possible Alzheimer’s disease. A multicenter U.S. study, the Imaging Dementia—Evidence for Amyloid Scanning (IDEAS) study, is evaluating the impact of imaging on diagnosis and management in these patients. Additional amyloid and tau imaging agents (some with reported more specific binding patterns) are in development.
Interpretation of Amyloid Imaging
The target binding site of amyloid agents is abnormal Aβ plaques in the cortex of the cerebral hemispheres. However these tracers also have nontarget/nonspecific binding at other sites, most prominently the cerebral white matter. Nontarget binding is reported as more common with the F-18 amyloid imaging agents, and for this reason agent-specific training programs have been developed to assist in image interpretation. Though the specific criteria for a positive (abnormal) scan vary slightly based on the imaging agent, the key finding is increased radiotracer binding in cerebral cortex, causing loss of gray-white matter distinction.
The following is an interpretation discussion with practice cases, focused on the first FDA-approved F-18 amyloid agent, florbetapir.
An abnormal florbetapir brain study is seen with either:
- Two or more areas (each larger than single cortical gyrus) with reduced or absent gray-white matter contrast due to increased cortical activity
-or-
- One or more areas with gray matter activity greater than adjacent white matter
An important point is that Aβ plaques are not specific for Alzheimer’s disease. So while a negative amyloid imaging study may exclude Alzheimer’s with high degree of certainty, a positive study does not confirm the diagnosis. I.e. the study has high sensitivity but lower specificity.
Below are 5 practice cases with F-18 Florbetapir:
References:
Mallik A et al. Clinical Amyloid Imaging. Semin Nucl Med 2017;47:31-43.
Amyvid package insert. https://pi.lilly.com/us/amyvid-uspi.pdf Eli Lilly and Co, 2013.
Amyvid Reader Training Program. https://amyvid.myregistrationp.com/amyvid/login.do