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

Moghbel, Mateen; Saboury, Babak; Basu, Sandip; Metzler, S.; Torigian, Drew A.; Långström, Bengt; Alavi, Abass

doi:10.1007/s00259-011-1960-4

Cited by 38 publications

(17 citation statements)

References 56 publications

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“…This hypothesis, which proposes that amyloid in its various forms—namely oligomers, fibrils, and neuritic plaques—are etiologically involved in AD has been widely held in the field for a number of decades, but has recently been challenged. Questions regarding the theoretical basis of PET amyloid imaging [7] were met with strenuous objections; advocates of the modality rejected the notion that the uncertainty of the amyloid hypothesis posed a potentially serious limitation, as the hypothesis was “not highly relevant to the feasibility and validity of Aβ imaging” [2]. …”

Section: (Iii) Aβ Imaging and Neuropathological Criteria For Ad Diagnmentioning

confidence: 99%

Amyloid-β Positron Emission Tomography Imaging Probes: A Critical Review

Kepe

Moghbel

Långström

et al. 2013

JAD

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The rapidly rising prevalence and cost of Alzheimer’s disease (AD) in recent decades has made the imaging of amyloid-β (Aβ) deposits the focus of intense research. Several amyloid imaging probes with purported specificity for Aβ plaques are currently at various stages of FDA approval. However, a number of factors appear to preclude these probes from clinical utilization. As the available “amyloid specific” PET imaging probes have failed to demonstrate diagnostic value and have shown limited utility for monitoring therapeutic interventions in humans, a debate on their significance has emerged. The aim of this review is to identify and discuss critically the scientific issues contributing to the extensive inconsistencies reported in the literature on their purported in vivo amyloid specificity and potential utilization in patients.

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Section: (Iii) Aβ Imaging and Neuropathological Criteria For Ad Diagnmentioning

confidence: 99%

Amyloid-β Positron Emission Tomography Imaging Probes: A Critical Review

Kepe

Moghbel

Långström

et al. 2013

JAD

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“…Moghbel et al reviewed the technical aspects and discussed several potential problems, such as partial volume effects that result in underestimated SUV data, high ratio of non-specific to specific uptake occurring in white matter, and discordance between the distribution of amyloid beta in the brain with histopathological and immunohistochemical studies. 33 For example, data from a recent phase 3 florbetapir study suggested that amyloid burden in the frontal lobe does not correlate strongly with histopathology determined through autopsy studies. 34 …”

Section: Amyloid Imagingmentioning

confidence: 99%

“…Also, questions concerning the evidence for the binding specificity have recently been raised, as PiB development occurred in the context of the the microdoses that would reach the targeted proteins in vivo, but binding studies were performed ex vivo in a medium with excess radiotracer. 33 …”

Section: Amyloid Imagingmentioning

confidence: 99%

Neuronuclear Imaging in the Evaluation of Dementia and Mild Decline in Cognition

Torosyan

Silverman

2012

Seminars in Nuclear Medicine

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Recently, the National Institute on Aging (NIA) and the Alzheimer’s Association (AA), identified specific structural and functional neuroimaging findings as valuable markers of biological processes occurring in the human brain -- especially, processes that herald impending dementia due to Alzheimer’s disease (AD), in its prodromal form. In particular, the imaging modalities of MRI and PET were singled out, along with certain biomarkers in cerebrospinal fluid (CSF), to serve this purpose. We review the clinical tests available for neuropsychologic evaluation and in cases when the differential diagnosis for the causes of cognitive impairment is difficult to make, we consider biomarkers, beginning with CSF, for assessment of cognitive decline. For more direct information about dementia-related pathologic changes in brain tissue, structural features observed in MRI scans are regarded. We next discuss the use of SPECT for evaluating functional changes. Then, pertinent to the recent NIA/AA consensus statement on the diagnosis of prodromal AD, we focus upon assessing the cerebral metabolic changes associated with neurodegenerative diseases that are identified with FDG-PET, as well as consider the most appropriate roles for amyloid imaging based upon recent studies examining the use of PET with tracers having higher retention in brain tissue harboring plaques comprised of insoluble beta-amyloid. We also consider leading causes for the current underutilization of neuronuclear imaging in evaluating patients with cognitive problems, along with strategies for combating them. Finally, we suggest an overall diagnostic algorithm to guide optimal use of all the neuroimaging tools in assessing patients with cognitive decline.

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“…CMS subsequently declined reimbursement based on "insufficient evidence to conclude that the use of positron emission tomography (PET) amyloid-beta (Aβ) imaging is reasonable and necessary for the diagnosis or treatment…….and thus PET Aβ imaging is not covered under §1862(a)(1)(A) of the Social Security Act ("the Act")." Over the past several years, we have emphasized the difficulties that are faced in characterizing the underlying causes of AD with PET [25,31,32]. This partly relates to the structural location of uptake of the agents that target these plaques and partly to their non-specific concentration in the adjacent tissues including the white matter.…”

Section: The Introduction Of 2-deoxy-2-[f-18]fluoro-d-glucose (Fdg) (mentioning

confidence: 99%

Suboptimal validity of amyloid imaging-based diagnosis and management of Alzheimer’s disease: why it is time to abandon the approach

Alavi

Barrio

Werner

et al. 2019

Eur J Nucl Med Mol Imaging

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

Cited by 38 publications

References 56 publications

Amyloid-β Positron Emission Tomography Imaging Probes: A Critical Review

Amyloid-β Positron Emission Tomography Imaging Probes: A Critical Review

Neuronuclear Imaging in the Evaluation of Dementia and Mild Decline in Cognition

Suboptimal validity of amyloid imaging-based diagnosis and management of Alzheimer’s disease: why it is time to abandon the approach

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