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The future of amyloid-beta imaging: a tale of radionuclides and tracer proliferation.

ABSTRACT: This review will focus on the coming proliferation of amyloid-beta imaging tracers and give an opinion on how the Alzheimer's disease field can develop a systematic means of evaluating which tracers are useful and how the useful tracers compare to each other.Several new tracers have been reported to be useful for human amyloid-beta imaging. The most recent of these are labeled with fluorine-18. Compared with the 20 min half-life of carbon-11 used in the most widely used tracer, Pittsburgh Compound-B, the 110 min half-life of fluorine-18 allows for wider utilization in research and clinical settings.It is likely that more than one fluorine-18-labeled tracer will come into common use. The use of preclinical and clinical 'bridging studies' to [C-11]Pittsburgh Compound-B could be a means to determine whether the sizable body of knowledge already gained in [C-11]Pittsburgh Compound-B studies can be applied to the understanding of these new tracers and to form a basis for the comparison among them. This approach could save resources and help sort out a potentially bewildering onslaught of new amyloid-beta imaging tracers.

SUBMITTER: Klunk WE

PROVIDER: S-EPMC2637561 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature

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The future of amyloid-beta imaging: a tale of radionuclides and tracer proliferation.

Klunk William E WE Mathis Chester A CA

Current opinion in neurology 20081201 6

<h4>Purpose of review</h4>This review will focus on the coming proliferation of amyloid-beta imaging tracers and give an opinion on how the Alzheimer's disease field can develop a systematic means of evaluating which tracers are useful and how the useful tracers compare to each other.<h4>Recent findings</h4>Several new tracers have been reported to be useful for human amyloid-beta imaging. The most recent of these are labeled with fluorine-18. Compared with the 20 min half-life of carbon-11 used ...[more]

PMID: 18989113

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Project description:BackgroundAmyloid β (Aβ) is thought to initiate a cascade of pathology culminating in Alzheimer's disease-related cognitive decline. Aβ accumulation in brain tissues may begin one to two decades prior to clinical diagnosis of Alzheimer's disease. Prior studies have demonstrated that Aβ detected in vivo with positron emission tomography with amyloid ligands (amyloid-PET) predicts contemporaneously measured cognition and future cognitive trajectories. Prior studies have not evaluated the added value of Aβ measures in predicting future cognition when repeated past cognitive measures are available. We evaluated the extent to which amyloid-PET improves prediction of future cognitive changes over and above predictions based only on sociodemographics and past cognitive measures.MethodsWe used data from participants in the University of California Davis Alzheimer's Disease Research cohort who were cognitively normal at baseline, participated in amyloid-PET imaging, and completed at least three cognitive assessments prior to amyloid-PET imaging (N = 132 for memory andN = 135 for executive function). We used sociodemographic and cognitive measures taken prior to amyloid-PET imaging to predict cognitive trajectory after amyloid-PET imaging and assessed whether measures of amyloid burden improved predictions of subsequent cognitive change. Improvements in prediction were characterized as percent reduction in the mean squared error (MSE) in predicted cognition post amyloid-PET and increase in percent variance explained.ResultsThe base model using only sociodemographics and past cognitive performance explained the majority of variance in both predicted memory measures (55.6%) and executive function measures (74.5%) following amyloid-PET. Adding amyloid positivity to the model reduced the MSE for memory by 0.2%, 95% CI: (0%, 2.6%), p = 0.48 and for executive function by 3.4%, 95% CI: (0.6%, 10.2%), p = 0.002. This corresponded to an increase in the percent variance explained of 0.1%, 95% CI: (0%, 1.2%) for memory and 0.9%, 95% CI: (0.1%, 2.8%) for executive function. Similar results were obtained using a continuous measure of amyloid burden.ConclusionIn this cohort, the addition of amyloid burden slightly improved predictions of executive function compared to models based only on past cognitive assessments and sociodemographics. When repeated cognitive assessments are available, the additional utility of amyloid-PET in predicting future cognitive impairment may be limited.

Project description:BackgroundThe deposition of β-amyloid (Aβ) in the brain is a biomarker of Alzheimer's disease (AD). Highly sensitive Aβ positron emission tomography (PET) imaging plays an essential role in diagnosing and evaluating the therapeutic effects of AD.AimTo synthesize a new Aβ tracer [18F]DRKXH1 (5-(4-(6-(2-[18]fluoroethoxy)ethoxy)imidazo[1,2-alpha]pyridin-2-yl)phenyl) and evaluate the tracer performance by biodistribution analysis, in vivo small-animal PET-CT dynamic scan, ex vivo and in vitro autoradiography, and PET in human subjects.Methods[18F]DRKXH1 was synthesized automatically by the GE FN module. Log D (pH 7.4) and biodistribution of [18F]DRKXH1 were investigated. Small-animal-PET was used for [18F]DRKXH1 and [18F]AV45 imaging study in AD transgenic mice (APPswe/PSEN1dE9) and age-matched normal mice. The distribution volume ratios (DVR) and standardized uptake value ratios (SUVRs) were calculated with the cerebellum as the reference region. The deposition of Aβ plaques in the brain of AD transgenic mice was determined by ex vivo autoradiography and immunohistochemistry. In vitro autoradiography was performed in the postmortem brain sections of AD patients and healthy controls. Two healthy control subjects and one AD patient was subjected to in vivo PET study using [18F]DRKXH1.ResultsThe yield of [18F]DRKXH1 was 40%, and the specific activity was 156.64 ± 11.55 GBq/μmol. [18F]DRKXH1 was mainly excreted through the liver and kidney. The small-animal PET study showed high initial brain uptake and rapid washout of [18F]DRKXH1. The concentration of [18F]DRKXH1 was detected in the cortex and hippocampus of AD transgenic mice brain. The cortex DVR of AD transgenic mice was higher than that of WT mice (P < 0.0001). Moreover, the SUVRs of AD transgenic mice were higher than those of WT mice based on the 0-60-min dynamic scanning. In vitro autoradiography showed a significant concentration of tracer in the Aβ plaque-rich areas in the brain of AD transgenic mice. The DVR value of [18F]-DRKXH1 is higher than that of [18F]-AV45 (1.29 ± 0.05 vs. 1.05 ± 0.08; t = 5.33, P = 0.0003). Autoradiography of postmortem human brain sections showed [18F]DRKXH1-labeled Aβ plaques in the AD brain. The AD patients had high retention in cortical regions, while healthy control subjects had uniformly low radioactivity uptake.Conclusions[18F]DRKXH1 is an Aβ tracer with high sensitivity in preclinical study and has the potential for in vivo detection of the human brain.

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The future of amyloid-beta imaging: a tale of radionuclides and tracer proliferation.

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The future of amyloid-beta imaging: a tale of radionuclides and tracer proliferation.

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