P1‐084: PET imaging of β‐amyloid with florpiramine F18 (18F‐AV‐45): Preliminary results from a phase II study of cognitively normal elderly subjects, individuals with mild cognitive impairment, and patients with a clinical diagnosis of Alzheimer's disease

Abstract

The development of an 18F amyloid imaging biomarker will facilitate the evaluation of individuals with late-life cognitive impairment, by distinguishing those free of AD pathology as evidenced by the absence of Aβ aggregates from those with substantial Aβ deposition in an AD-like pattern. Preliminary studies demonstrated the ability of florpiramine to detect cerebral amyloid with a test-retest variance of 5.1% in AD patients and 2.2% in cognitively normal subjects. Objective: The objective of this study was evaluate the performance characteristics of florpiramine in individuals with probable Alzheimer's disease (AD), mild cognitive impairment (MCI) and normal cognitively intact elderly subjects (NC). Subjects meeting established diagnostic criteria for NC (78), MCI (60), or AD (45), received a clinical, cognitive, and functional evaluation using standardized assessment methods and a 10 minute PET image, acquired 50 minutes following iv injection of 10 mCi (370 MBq) of 18F-AV-45. PET images were rated visually without knowledge of the subject's age or clinical category, on the basis of overall ligand retention in cortical gray matter (scale 0 - 4). In addition, a semi-automated algorithm calculated standard uptake values (SUV) in pre-defined anatomically relevant cortical regions, relative to cerebellar gray matter (SUVr). Demographic of the cohort are listed in Table 1. Mean 18F-AV-45 retention values in cortical gray matter for the NC and AD groups differed significantly (p<0.001) for both the blinded visual PET rating and the automated SUVr values. As expected, there was overlap in florpiramine retention between some subjects in the AD and NC groups. Values for subjects in the MCI group were intermediate those in the NC and AD groups. In general, 18F-AV-45 retention tended to increase with increasing age of the subject. Florpiramine (18F-AV-45) is a sensitive marker for the presence of amyloid in cortical gray matter in elderly individuals, and can differentiate groups of subjects meeting standard diagnostic criteria for AD, MCI, and normal cognitive function. Given the known prevalence of amyloid pathology in cognitively normal older subjects, this information may be of greatest clinical utility when demonstrating the absence of amyloid, thus ruling out AD, in patients undergoing evaluation for late-life cognitive impairment.