Amyloid Imaging with¹⁸F-Florbetaben in Alzheimer Disease and Other Dementias

Abstract

Amyloid imaging with 18 F-labeled radiotracers will allow widespread use, facilitating research, diagnosis, and therapeutic development for Alzheimer disease. The purpose of the study program was to compare cortical amyloid deposition using 18 F-florbetaben and PET in controls and subjects with mild cognitive impairment (MCI), frontotemporal lobar degeneration (FTLD), dementia with Lewy bodies (DLB), vascular dementia (VaD), Parkinson disease (PD), and Alzheimer disease (AD). Methods: One hundred nine subjects in 3 clinical studies at Austin Health were reviewed: 32 controls, 20 subjects with MCI, and 30 patients with AD, 11 with FTLD, 7 with DLB, 5 with PD, and 4 with VaD underwent PET after intravenous injection of 300 MBq of 18 F-florbetaben. Standardized uptake value ratios (SUVR) using the cerebellar cortex as a reference region were calculated between 90 and 110 min after injection. Results: When compared with the other groups, AD patients demonstrated significantly higher SUVRs (P , 0.0001) in neocortical areas. Most AD patients (96%) and 60% of MCI subjects showed diffuse cortical 18 F-florbetaben retention. In contrast, only 9% of FTLD, 25% of VaD, 29% of DLB, and no PD patients and 16% of controls showed cortical binding. Although there was a correlation between Mini Mental State Examination and b-amyloid burden in the MCI group, no correlation was observed in controls, FTLD or AD. Conclusion: 18 F-florbetaben had high sensitivity for AD, clearly distinguished patients with FTLD from AD, and provided results comparable to those reported with 11 C-Pittsburgh Compound B in a variety of neurodegenerative diseases.

Amyloid Imaging: Poised for Integration into Medical Practice

“…This study also demonstrated the ability of diagnosing AD from other neurodegenerative disorders (p < 0.001), including vascular dementia, DLB, and frontotemporal lobar dementia [38]. A phase 0 trial demonstrated the safety and efficacy of this drug.…”

Imaging in Parkinson's Disease

“…Amyloid burden in PDD patients is heterogeneous with cases of PDD, where amyloid deposition overlaps with the levels observed in healthy subjects and in PD patients (Edison et al, 2013(Edison et al, , 2008Foster et al, 2010;Gomperts et al, 2012Gomperts et al, , 2008Jokinen et al, 2010;Maetzler et al, 2009Maetzler et al, , 2008 and other cases of PDD showing elevated cortical amyloid deposition in the Alzheimer's disease (AD) range (Edison et al, 2013(Edison et al, , 2008Foster et al, 2010;Gomperts et al, 2012;Jokinen et al, 2010;Maetzler et al, 2009Maetzler et al, , 2008Shimada et al, 2013). In contrast, amyloid burden is usually elevated in DLB patients compared to healthy subjects and PD patients and the incidence ranges between 33% and 100% (Burke et al, 2011;Claassen, Lowe, Peller, Petersen, & Josephs, 2011;Edison et al, 2008;Foster et al, 2010;Gomperts et al, 2012Gomperts et al, , 2008Graff-Radford et al, 2012;Kantarci et al, 2012;Maetzler et al, 2009Maetzler et al, , 2008Rowe et al, 2007;Siderowf et al, 2014;Villemagne et al, 2011).…”

“…However, extracellular Aβ-amyloid plaques and intracellular tau neurofibrillary tangle are also observed at autopsy in PD, PDD, and DLB patients (Horvath, Herrmann, Burkhard, Bouras, & K€ ovari, 2013;Jellinger & Attems, 2008;Jellinger, Seppi, Wenning, & Poewe, 2002 of amyloid deposition in PD, PDD, and DLB. Overall these studies found that amyloid deposition tends to be modest in PD with normal cognition occurring in about 0%-13% of PD patients (Edison et al, 2013(Edison et al, , 2008Foster et al, 2010;Gomperts et al, 2012Gomperts et al, , 2008Johansson et al, 2008;Jokinen et al, 2010;Maetzler et al, 2009;Siderowf et al, 2014;Villemagne et al, 2011). Amyloid burden is generally low in PD subjects with mild cognitive impairment (MCI), and does not distinguish cognitively normal PD patients from PD-MCI (Foster et al, 2010;Gomperts et al, 2012Gomperts et al, , 2013Petrou et al, 2012).…”

“…Global amyloid deposition has been associated to worse cognitive performance (Foster et al, 2010;Gomperts et al, 2013;Petrou et al, 2012;Villemagne et al, 2011), and the absence of cortical amyloid deposition was associated with a better response to ACh inhibitors (Burke et al, 2011). The clinical significance of amyloid burden in Lewy bodies diseases is still unclear, but it has been suggested that early and significant cortical amyloid burden may accelerate cognitive decline as a result of synergistic Aβ-α-synuclein neurotoxicity.…”

Amyloid-β imaging with PET in Alzheimer’s disease: is it feasible with current radiotracers and technologies?

“…However, the advent of three new radiotracers, which are currently at various stages of FDA assessment and approval, has brought amyloid imaging to the doorstep of clinical use. Recent clinical studies on florbetapir (AV-45), florbetaben (BAY-94), and flutemetamol (GE-067) claim to have demonstrated an ability to discriminate between AD patients and healthy controls with high degrees of sensitivity and specificity [6][7][8][9][10][11]. However, the theoretical bases of and ubiquitous patterns in the reported data raise a host of lingering questions that should be addressed before these radiotracers are clinically approved.…”