18F] Flutemetamol PET imaging for beta-amyloid deposition across the spectrum of Alzheimer's disease

Abstract

We had demonstrated that a diagnostic framework with a beta amyloid (Aβ) deposition by [11C]-PIB PET allows for an earlier Alzheimer's disease (AD) diagnosis. The PET amyloid imaging with a tracer of [18F]-labeled PIB derivate [18F]-Flutemetamol (FMM) have recently developed to be a novel technology of underlying AD pathology. The aim is to identify the Aβ deposition by [18F]-FMM PET across the spectrum of AD. Twenty-eight patients with AD, 44 with mild cognitive impairment (MCI) and 32 subjects with healthy control (HC) were studied. All 104 subjects (age: 55–89 years) underwent 30-min static [18F]-FMM PET, acquired 85 min after injection (196.4 ± 6.6 MBq), and cognitive test. [18F]-FMM scans were assessed visually with 3 blind readers as abnormal or normal cortical uptake. The standardized uptake value ratios (SUVR) were defined quantitatively in regions of interest defined on co-registered MRI (cerebellar gray as a reference region). The visual assessments of [18F]-FMM scans had an increased uptake in 27 of 28 scans with AD and 4 of 32 scans with HC, corresponding to an overall sensitivity of 96.4% and a specificity of 87.7%. Inter-reader agreement was excellent (Kappa score=0.84), and intra-reader agreement was 93.3%. Fourteen (31.8%) of 44 MCI scans showed an increased uptake of [18F]-FMM. The FMM SUVR of composite cortical regions in AD was significantly greater than in HC (1.84 ± 0.27 vs 1.28 ± 0.17, P<0.01). MCI patients had a bimodal distribution of SUVR. The FMM SUVR in 14 patients with [18F]-FMM positive MCI and 30 patients with negative MCI were 1.82 ± 0.29 and 1.20 ± 0.08, respectively. The regional FMM SUVR of all cortical regions in AD, except for medial temporal cortex, were significantly different from HC. Cortical FMM SUVR was significantly correlated negatively with MMSE scores (r=−0.62, P<0.01), and positively to CDR SB scores (r=0.55, P<0.01) when all groups were analyzed. [18F]-Flutemetamol PET discriminates Alzheimer's disease from healthy controls and facilitates integration of Aβ imaging into clinical practice. The PET imaging with [18F]-Flutemetamol is a reliable biomarker of Aβ deposition along the continuum from normal cognitive status to dementia of AD.