Amyloid PET Ligands for Dementia

Villemagne, Victor L.; Rowe, Christopher C.

doi:10.1016/j.cpet.2009.12.008

Cited by 24 publications

(9 citation statements)

References 217 publications

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“…18 FFlorbetaben (Rowe et al, 2008), 18 F-Flutemetamol (Vandenberghe et al, 2010), 18 F-Florbetapir (Wong et al, 2010) and 18 F-AZD4694 (Jureus et al, 2010) (Figure 1). The different pharmacokinetic and pharmacodynamic characteristics of these radiotracers are discussed in detail elsewhere (Villemagne and Rowe, 2010).…”

Section: Amyloid Ligandsmentioning

confidence: 99%

Amyloid imaging

Villemagne

Rowe

2011

Int. Psychogeriatr.

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Molecular neuroimaging techniques such as PET are proving valuable in the early and differential diagnosis of Alzheimer's disease (AD).With the advent of new therapeutic strategies aimed at reducing β-amyloid (Aβ) burden in the brain to potentially prevent or delay functional and irreversible cognitive loss, there is increased interest in developing agents that allow assessment of Aβ burden in vivo. Amyloid imaging with PET has proven useful in the discrimination of dementias, showing significantly higher Aβ burden in the gray matter of AD patients when compared with healthy controls or patients with frontotemporal dementia. ApoE ε4 carriers, independent of diagnosis or disease severity, present with higher Aβ burden than non-ε4 carriers. Amyloid imaging matches histopathological reports in aging and dementia, reflecting the true regional density of Aβ plaques in cortical areas. It also appears to be more sensitive than FDG-PET for the diagnosis of AD. In healthy older people there is an increasing prevalence of amyloid positive scans with age, rising from 20% in the seventh decade to 60% in the ninth decade. Of people with mild cognitive impairment (MCI), 40-60% present with detectable cortical Aβ deposition. In both groups, Aβ deposition is associated with a higher risk for cognitive decline and dementia due to AD. These observations suggest that Aβ deposition is not part of normal aging, supporting the hypothesis that it occurs well before the onset of symptoms and is likely to represent preclinical AD in asymptomatic persons and prodromal AD in MCI. Further longitudinal observations, coupled with different disease-specific tracers and biomarkers, are required to confirm this hypothesis and further elucidate the precise role of Aβ deposition in the course of AD.

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Section: Amyloid Ligandsmentioning

confidence: 99%

Amyloid imaging

Villemagne

Rowe

2011

Int. Psychogeriatr.

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“…Unfortunately, the radioactive decay half-life of 11 C is 20 min, which limits the use of PiB to centres with an onsite cyclotron and 11 C radiochemistry expertise, making access to PiB PET restricted and the costs prohibitive for routine clinical use [15]. To overcome these limitations, several tracers labelled with 18 F (half-life 110 min) that permit centralized production and regional distribution, as currently practiced worldwide in the supply of FDG for clinical use, have been synthesized and tested [16][17][18][19][20].…”

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Comparison of 11C-PiB and 18F-florbetaben for Aβ imaging in ageing and Alzheimer’s disease

Villemagne

Mulligan

Pejoska

et al. 2012

Eur J Nucl Med Mol Imaging

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170

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“…These proposals have argued that when there is a clear history of progressive cognitive decline, objective evidence from psychometric tests of episodic memory impairment, and characteristic abnormalities in the cerebrospinal fluid or neuroimaging studies such as amyloid imaging, dementia might not be required for the diagnosis of probable AD (11,12). Thus, as the criteria for the diagnosis of AD evolve, Ab imaging is likely to have an increasingly important role in clinical practice provided it is accessible and affordable (13).…”

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confidence: 99%

“…Consequently, access to 11 C-PiB PET is restricted, and the high cost of studies is prohibitive for routine clinical use. To overcome these limitations, several tracers labeled with 18 F (half-life, 110 min), permitting centralized production and regional distribution, were synthesized and tested (13)(14)(15)(16)(17).…”

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Amyloid Imaging with¹⁸F-Florbetaben in Alzheimer Disease and Other Dementias

Villemagne¹,

Ong²,

Mulligan³

et al. 2011

J Nucl Med

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324

272

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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.

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Amyloid PET Ligands for Dementia

Cited by 24 publications

References 217 publications

Amyloid imaging

Amyloid imaging

Comparison of 11C-PiB and 18F-florbetaben for Aβ imaging in ageing and Alzheimer’s disease

Amyloid Imaging with¹⁸F-Florbetaben in Alzheimer Disease and Other Dementias

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Amyloid PET Ligands for Dementia

Cited by 24 publications

References 217 publications

Amyloid imaging

Amyloid imaging

Comparison of 11C-PiB and 18F-florbetaben for Aβ imaging in ageing and Alzheimer’s disease

Amyloid Imaging with18F-Florbetaben in Alzheimer Disease and Other Dementias

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Amyloid Imaging with¹⁸F-Florbetaben in Alzheimer Disease and Other Dementias