A PubMed search of reports, published before April, 2011, for this Rapid Review was done using the key words “positron” and “amyloid”, and specific searches were also done for the tracer names “flutemetamol”, “florbetapir”, “florbetaben”, “AV-45”, “AV-1”, “GE-067”, “BAY-94-9172”, and “FDDNP”. All clinically relevant papers relating to compounds currently in formal clinical trials were included, and other citations were selected only if essential for this Rapid Review. Only articles
Rapid ReviewClinical amyloid imaging in Alzheimer's disease
Introduction
In the next few decades, extraordinary efforts will be spent on the prevention and treatment of dementia, because this illness will affect about 63 million people by 2030, and 114 million by 2050 worldwide.1 One treatment strategy will probably involve anti-amyloid agents: appropriate animal models exist that could lead to the generation of effective compounds. For such agents to be effective, they would need to be given early in the disease course before degeneration has become too advanced. Although early clinical phenotypes, such as mild cognitive impairment (MCI),2 have been explored, only some patients actually progress to dementia; therefore, additional markers of prognosis and underlying pathology are needed to identify patients early in the disease course.3 Furthermore, in clinical trials, response to anti-amyloid agents will probably be very slow and clinical outcome might also be subject to factors unrelated to amyloid deposition, making trials involving patients with MCI extremely time consuming and costly; therefore, early, direct in-vivo measurements of the treatment target might be desirable so that further clinical testing of anti-amyloid drugs that do not affect their target mechanism could be halted. Among possible markers of early Alzheimer's disease (AD), the Pittsburgh compound B (PiB) seems to be a sensitive and specific marker of amyloid-β deposition.4 This ability to image amyloid-β deposition has stimulated the development of several other potential amyloid-β ligands in the hope of advancing early diagnosis and treatment of AD. In this Rapid Review, we discuss the current state of research into PET amyloid imaging tracers.
Section snippets
Pittsburgh compound B
Most amyloid imaging in human beings is currently done in research studies with the 11C-labelled PET tracer PiB.5 However, the very short physical half-life (20 min) of 11C requires that a cyclotron be available on-site for production of the isotope, which prevents widespread clinical use. PiB binds to insoluble fibrillary amyloid β with high affinity, but not to amorphous amyloid plaques and neurofibrillary tangles. Non-specific (ie, non-displaceable) binding is seen mainly in white matter.
18F-labelled tracers
Three 18F-labelled tracers are being investigated in clinical trials; they have been developed as proprietary tracers for commercial distribution, which is possible because of the 110 min physical half-life of 18F. Flutemetamol (GE-067) is the 3′-fluoro-derivative of PiB, whereas florbetaben (BAY-94-9172, AV-1) and florbetapir (AV-45) are stilbene and styrylpyridine derivatives, which exhibit high-affinity binding for fibrillary amyloid similar to PiB (table);20, 21, 22, 23, 24, 25, 26 they
Conclusions and future directions
The data discussed here suggest that all three 18F-labelled amyloid ligands undergoing clinical trials could be used to detect fibrillary amyloid in patients with AD with high sensitivity. Lipophilic plasma metabolites, which have been reported for two tracers, could increase non-specific background activity and thus reduce the contrast between normal cortex and amyloid. Higher non-specific uptake in white matter does not seem to interfere substantially with visual image interpretation, because
Search strategy and selection criteria
References (47)
- et al.
Amyloid imaging results from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging
Neurobiol Aging
(2010) - et al.
PET imaging of amyloid deposition in patients with mild cognitive impairment
Neurobiol Aging
(2008) - et al.
11C-PiB PET assessment of change in fibrillar amyloid-beta load in patients with Alzheimer's disease treated with bapineuzumab: a phase 2, double-blind, placebo-controlled, ascending-dose study
Lancet Neurol
(2010) - et al.
Quantification of βA4 protein deposition in the medial temporal lobe: a comparison of Alzheimer's disease and senile dementia of Lewy body type
Neurosci Lett
(1992) - et al.
Imaging of amyloid [beta] in Alzheimer's disease with 18F-BAY94-9172, a novel PET tracer: proof of mechanism
Lancet Neurol
(2008) - et al.
Whole-body biodistribution and brain PET imaging with [18F]AV-45, a novel amyloid imaging agent—a pilot study
Nucl Med Biol
(2010) - et al.
Cerebral amyloid-β PET with florbetaben (18F) in patients with Alzheimer's disease and healthy controls: a multicentre phase 2 diagnostic study
Lancet Neurol
(2011) - et al.
Voxel-based analysis of Alzheimer's disease PET imaging using a triplet of radiotracers: PIB, FDDNP, and FDG
NeuroImage
(2010) - et al.
The diagnosis of dementia due to Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease
Alzheimers Dement
(2011) - et al.
Revising the definition of Alzheimer's disease: a new lexicon
Lancet Neurol
(2010)