Langbaum JB, Chen K, Fleisher AS, Keppler J, Prouty A, Bandy D, Perkins M, Richter NK, Jakimovich L, Reiman EM.
[18F]AZD4694 in the symptomatic and presymptomatic study of Alzheimer's disease.
Human Amyloid Imaging 2011 Meeting Abstracts. 2011 Jan 15;
Background and Objective: Fibrillar amyloid-s (As) PET ligands offer great promise in the scientific study, early
detection, tracking, and differential diagnosis of Alzheimer's disease (AD) and the evaluation of As-modifying
treatments. [F18]AZD4694, a second-generation ligand developed by AstraZeneca, is used in the present study to
characterize fibrillar As burden in patients with mild AD, healthy elderly and healthy younger controls.
Methods: 90min dynamic PET scans were acquired following the administration of [18F]AZD4694 10 mCi IV
in 6 patients with probable mild AD (2 apolipoprotein E (APOE) ε4 carriers, 4 non-carriers), 9 healthy elderly
adults (5 APOE ε4 carriers, 4 non-carriers), and 5 healthy younger APOE ε4 non-carriers. Fibrillar As burden
was alternatively quantified using cerebral-to-cerebellar standard uptake value ratios (SUVRs) versus distribution
volume ratios (DVRs), data from the 27-39min versus 0-90min frames, blind visual ratings, and gray matter, white
matter, and cerebellar time-activity curves (TACs).
Results: Our findings provide additional support of the following observations: 1) [18F]AZD4694 reaches
equilibrium relatively quickly (about 27min following radiotracer administration). 2) There is a high specific binding
in AD cerebral cortex, relatively low non-specific binding in white matter, intermediate (higher than background)
binding in pons, and easy assessment of fibrillar As burden using visual ratings. 3) 21-33min SUVR images are
roughly similar to 21-33min DVR, 0-90min SUVR, and 0-90min DVR images in their ability to distinguish fibrillar As
from background uptake and to distinguish between subjects in the probable AD, healthy elderly APOE ε4 carrier,
and healthy elderly and younger ε4 non-carrier groups.
Conclusions: [18F]AZD4694 PET offers promise in the assessment of fibrillar As deposition. Additional studies
are needed to compare it to other ligands and determine the extent to which it offers improved sensitivity for the
pre-symptomatic detection and tracking of AD.