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Amyloid PET imaging in Alzheimer's disease: a comparison of three radiotracers.

ABSTRACT: The increasing use of amyloid PET in Alzheimer's disease research and clinical trials has motivated efforts to standardize methodology. We compared retention of the (11)C radiotracer Pittsburgh Compound B (PiB) and that of two (18)F amyloid radiotracers (florbetapir and flutemetamol) using two study populations. We also examined the feasibility of converting between tracer-specific measures, using PiB as the common link between the two (18)F tracers.One group of 40 subjects underwent PiB and flutemetamol imaging sessions and a separate group of 32 subjects underwent PiB and florbetapir imaging sessions. We compared cortical and white matter retention for each (18)F tracer relative to that of PiB, as well as retention in several reference regions and image analysis methods. Correlations between tracer pairs were used to convert tracer-specific threshold values for amyloid positivity between tracers.Cortical retention for each pair of tracers was strongly correlated regardless of reference region (PiB-flutemetamol, ??=?0.84-0.99; PiB-florbetapir, ??=?0.83-0.97) and analysis method (??=?0.90-0.99). Compared to PiB, flutemetamol had higher white matter retention, while florbetapir had lower cortical retention. Two previously established independent thresholds for amyloid positivity were highly consistent when values were converted between tracer pairs.Despite differing white and grey matter retention characteristics, cortical retention for each (18)F tracer was highly correlated with that of PiB, enabling conversion of thresholds across tracer measurement scales with a high level of internal consistency. Standardization of analysis methods and measurement scales may facilitate the comparison of amyloid PET data obtained using different tracers.

SUBMITTER: Landau SM

PROVIDER: S-EPMC4055504 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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Amyloid PET imaging in Alzheimer's disease: a comparison of three radiotracers.

Landau S M SM Thomas B A BA Thurfjell L L Schmidt M M Margolin R R Mintun M M Pontecorvo M M Baker S L SL Jagust W J WJ

European journal of nuclear medicine and molecular imaging 20140320 7

<h4>Purpose</h4>The increasing use of amyloid PET in Alzheimer's disease research and clinical trials has motivated efforts to standardize methodology. We compared retention of the (11)C radiotracer Pittsburgh Compound B (PiB) and that of two (18)F amyloid radiotracers (florbetapir and flutemetamol) using two study populations. We also examined the feasibility of converting between tracer-specific measures, using PiB as the common link between the two (18)F tracers.<h4>Methods</h4>One group of 4 ...[more]

PMID: 24647577

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Project description:IntroductionThere is a growing need in clinical research domains for direct comparability between amyloid-beta (Aβ) Positron Emission Tomography (PET) measures obtained via different radiotracers and processing methodologies. Previous efforts to provide a common measurement scale fail to account for non-linearities between measurement scales that can arise from these differences. We introduce a new application of distribution mapping, based on well established statistical orthodoxy, that we call Nonlinear Distribution Mapping (NoDiM). NoDiM uses cumulative distribution functions to derive mappings between Aβ-PET measurements from different tracers and processing streams that align data based on their location in their respective distributions.MethodsUtilizing large datasets of Florbetapir (FBP) from the Alzheimer's Disease Neuroimaging Initiative (n = 349 female (%) = 53) and Pittsburgh Compound B (PiB) from the Harvard Aging Brain Study (n = 305 female (%) = 59.3) and the Australian Imaging, Biomarker & Lifestyle Flagship Study of Ageing (n = 184 female (%) = 53.3), we fit explicit mathematical models of a mixture of two normal distributions, with parameter estimates from Gaussian Mixture Models, to each tracer's empirical data. We demonstrate the accuracy of these fits, and then show the ability of NoDiM to transform FBP measurements into PiB-like units.ResultsA mixture of two normal distributions fit both the FBP and PiB empirical data and provides a strong basis for derivation of a transfer function. Transforming Aβ-PET data with NoDiM results in FBP and PiB distributions that are closely aligned throughout their entire range, while a linear transformation does not. Additionally the NoDiM transform better matches true positive and false positive profiles across tracers.DiscussionThe NoDiM transformation provides a useful alternative to the linear mapping advocated in the Centiloid project, and provides improved correspondence between measurements from different tracers across the range of observed values. This improved alignment enables disparate measures to be merged on to continuous scale, and better enables the use of uniform thresholds across tracers.

Project description:BackgroundMetabotropic glutamate subtype 5 receptors (mGluR5) modulate synaptic transmission and may constitute an important therapeutic target in Alzheimer's disease (AD) by mediating the synaptotoxic action of amyloid-β oligomers. We utilized the positron emission tomography (PET) radioligand [18F]FPEB to investigate mGluR5 binding in early AD.MethodsSixteen individuals with amnestic mild cognitive impairment (MCI) due to AD or mild AD dementia who were positive for brain amyloid were compared to 15 cognitively normal (CN) participants who were negative for brain amyloid. Diagnostic groups were well balanced for age, sex, and education. Dynamic PET scans were acquired for 60 min, starting at 60 min after the initial administration of up to 185 MBq of [18F]FPEB using a bolus-plus-constant-infusion method (Kbol = 190 min). Equilibrium modeling with a cerebellum reference region was used to estimate [18F]FPEB binding (BPND) to mGluR5. Analyses were performed with and without corrections for gray matter atrophy and partial volume effects.ResultsLinear mixed model analysis demonstrated a significant effect of group (p = 0.011) and the group × region interaction (p = 0.0049) on BPND. Post hoc comparisons revealed a significant reduction (43%) in mGluR5 binding in the hippocampus of AD (BPND = 0.76 ± 0.41) compared to CN (BPND = 1.34 ± 0.58, p = 0.003, unpaired t test) participants, and a nonsignificant trend for a reduction in a composite association cortical region in AD (BPND = 1.57 ± 0.25) compared to CN (BPND = 1.86 ± 0.63, p = 0.093) participants. Exploratory analyses suggested additional mGluR5 reductions in the entorhinal cortex and parahippocampal gyrus in the AD group. In the overall sample, hippocampal mGluR5 binding was associated with episodic memory scores and global function.Conclusions[18F]FPEB-PET revealed reductions in hippocampal mGluR5 binding in early AD. Quantification of mGluR5 binding in AD may expand our understanding of AD pathogenesis and accelerate the development of novel biomarkers and treatments.

Dataset Information

Amyloid PET imaging in Alzheimer's disease: a comparison of three radiotracers.

Publications

Amyloid PET imaging in Alzheimer's disease: a comparison of three radiotracers.

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