Amyloid PET Findings in Alzheimer's Disease and Related Disorders

1) To discuss methodological aspects of fibrillary beta-amyloid PET imaging. 2) To learn about practical interpretation of fibrillary beta-amyloid PET imaging. 3) To understand the long duration of prodromal phase of amyloidopathy and its importance of correlating it with clinical symptoms when reporting on amyloid PET studies. 4) To review the presence of amyloidopathy in non-Alzheimer dementias. 5) The discuss appropriate use criteria for amyloid PET in clinical practice.

The recent developments of radioligands that visualize fibrillary β-amyloid offer a novel opportunity to study in vivo amyloid protein aggregation. [C-11]-Pittsburgh compound B (PiB) is a widely used investigational PET Aβ-amyloid ligand; More recently, amyloid PET has been used increasingly in clinical trials for AD therapeutics. Because the short 20-minute half-life of C-11 limits routine clinical use of PiB as a result of the need for an onsite cyclotron, amyloid-binding radiopharmaceuticals labeled with longer lived fluorine-18, with a 110-minute half-life, were developed and commercialized for wide availability. Several of such F-18 compounds, such as florbetapir, flutemetamol and florbetapen achieved approval by the U.S. Food and Drug Administration. The longer half-life of the F-18 compounds allow also more simplified delayed imaging acquisitions. Image interpretation of fibrillary β-amyloid scan will require reader's expertise to recognize the non-specific pattern of white matter radioligand uptake and to distinguish this form gray matter cortical uptake. Readers should also be aware that the build-up of the amyloid protein in Alzheimer disease may precede the clinical development of dementia with up to 15-20 years (so-called preclinical and prodromal phases). In other words, abnormal amyloid build-up can be seen in otherwise cognitive normal individuals. Therefore, scan interpretation should incorporate information of the clinical setting. Readers should also be familiar with novel definition of Alzheimer disease that now for the first time incorporate the use of imaging biomarkers, such as amyloid PET. Recently, a joint committee of the Society of Nuclear Medicine and the Alzheimers Association developed appropriate use criteria (AUC) to allow more judicious use of this new technology. Alzheimer pathology can also be seen with other dementia, such as dementia with Lewy bodies (DLB). Frontotemporal dementia is not characterized by significant amyloidopathy.

RC811B

Amyloid PET Findings in Alzheimer's Disease and Related Disorders