Amyloid PET Screening for Enrollment into Alzheimer’s Disease Clinical Trials: Initial Experience in a Phase 1b Clinical Trial (P3.207)

OBJECTIVE: We report our ongoing experience with amyloid positron emission tomography (PET) imaging as a screening tool in patients with prodromal or mild Alzheimer9s disease (AD). BACKGROUND: Amyloid PET imaging is being adopted as a method of AD clinical trial enrichment. DESIGN/METHODS: Patients fulfilling criteria for either prodromal or mild AD in a multicenter, Phase 1b clinical trial underwent florbetapir PET scanning at screening. PET, magnetic resonance imaging (MRI), and co-registered PET/MRI scans were reviewed by two independent readers and binary visual readings tabulated. Ten duplicate cases were presented to the readers to allow for calculation of intra-reader agreement statistics. Results were compared with semi-quantitative standard uptake value (SUV) ratios using a threshold of 1.10 to classify amyloid-negative from amyloid-positive patients. RESULTS: Of the first 199 PET/MRI scans reviewed, 19 discordant cases were identified when comparing visual readings to quantitative results: 17 with negative visual readings but positive quantitative results (composite SUV ratios 1.100-1.371) and 2 with positive visual readings but negative quantitative results (composite SUV ratios 1.052 and 1.089). Inter- and intra-reader Kappa scores from visual readings were 0.96 and 1, respectively. Of those patients who met all study clinical and laboratory inclusion and exclusion criteria, 40% were ultimately excluded due to an amyloid-negative PET scan based on visual readings. CONCLUSIONS: High inter- and intra-reader reliability was achieved. Factors potentially contributing to the high reliability were: a) availability of co-registered PET/MRI scans; b) harmonized spatial resolution and image orientation regardless of scanner model or patient position; c) 20-minute rather than 10-minute acquisition providing better statistics/less noise; and d) dynamic acquisition allowing motion correction. Agreement between visual and quantitative readings was good (90%). These data demonstrate that amyloid PET imaging can be an effective and feasible tool to enrich AD clinical trials in amyloid-positive patients, in particular in those patients at earlier stages of the disease process. Supported by: The study was funded by Biogen Idec. Disclosure: Dr. Sevigny has received personal compensation for activities with Biogen Idec. Dr. Suhy has received personal compensation for activities with Synarc Inc. as an employee. Dr. Chiao has received personal compensation for activities with Biogen Idec as an employee. Dr. Klein has received personal compensation for activities with Synarc Inc. as an employee. Dr. Oh has received personal compensation for activities with Synarc Inc. as an employee. Dr. Purcell has received personal compensation for activities with Synarc Inc. as an employee. Dr. Sampat has received personal compensation for activities with Synarc Inc. Dr. Barakos has received personal compensation for activities with Synarc, Inc.