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- Hirvonen, J, et al.
(författare)
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Measurement of striatal and extrastriatal dopamine transporter binding with high-resolution PET and [11C]PE2I: quantitative modeling and test-retest reproducibility
- 2008
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Ingår i: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 0271-678X. ; 28:5, s. 1059-1069
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Tidskriftsartikel (refereegranskat)abstract
- [11C]PE2I is a novel positron emission tomography (PET) radiotracer for the dopamine transporter (DAT). The reproducibility and reliability of [11C]PE2I measurements, especially in the small DAT-rich brain regions, is unknown and of critical importance to the interpretation of the data. Five healthy volunteers were scanned twice during the same day using [11C]PE2I and the HRRT PET scanner. Methods based on metabolite-corrected arterial plasma curve and reference region were used to estimate distribution volumes ( VT) and binding potential ( BP). Within-subject and between-subject variabilities were compared. [11C]PE2I accumulated in the DAT-rich striatum and the midbrain. Equilibrium of specific binding appeared late in the striatum, whereas it was reached earlier in the midbrain. Plasma metabolite analysis showed that the potentially brain-penetrant 4-hydroxymethyl metabolite represented 15% to 20% of total plasma radioactivity. VT and BP measurements were associated with low within-subject variability. Measurement of DAT binding in small brain regions, including the substantia nigra, is reproducible and reliable using [11C]PE2I and high-resolution research tomograph. A scanning time of more than 70 mins is required for the striatum, while less is sufficient for DAT quantification in the midbrain. The previously suggested involvement of the potentially brain-penetrant radioactive metabolite in the quantification should be further studied.
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- Snellman, Anniina, et al.
(författare)
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ASIC-E4: Interplay of Beta-Amyloid, Synaptic Density and Neuroinflammation in Cognitively Normal Volunteers With Three Levels of Genetic Risk for Late-Onset Alzheimer's Disease - Study Protocol and Baseline Characteristics
- 2022
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Ingår i: Frontiers in Neurology. - : Frontiers Media SA. - 1664-2295. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background:& nbsp;Detailed characterization of early pathophysiological changes in preclinical Alzheimer's disease (AD) is necessary to enable development of correctly targeted and timed disease-modifying treatments. ASIC-E4 study ( "Beta-Amyloid, Synaptic loss, Inflammation and Cognition in healthy APOE epsilon 4 carriers ") combines state-of-the-art neuroimaging and fluid-based biomarker measurements to study the early interplay of three key pathological features of AD, i.e., beta-amyloid (A beta) deposition, neuroinflammation and synaptic dysfunction and loss in cognitively normal volunteers with three different levels of genetic (APOE-related) risk for late-onset AD.& nbsp;Objective:& nbsp;Here, our objective is to describe the study design, used protocols and baseline demographics of the ASIC-E4 study.& nbsp;Methods/Design:& nbsp;ASIC-E4 is a prospective observational multimodal imaging study performed in Turku PET Centre in collaboration with University of Gothenburg. Cognitively normal 60-75-year-old-individuals with known APOE epsilon 4/epsilon 4 genotype were recruited via local Auria Biobank (Turku, Finland). Recruitment of the project has been completed in July 2020 and 63 individuals were enrolled to three study groups (Group 1: APOE epsilon 4/epsilon 4, N = 19; Group 2: APOE epsilon 4/epsilon 3, N = 22; Group 3: APOE epsilon 3/epsilon 3, N = 22). At baseline, all participants will undergo positron emission tomography imaging with tracers targeted against A beta deposition (C-11-PIB), activated glia (C-11-PK11195) and synaptic vesicle glycoprotein 2A (C-11-UCB-J), two brain magnetic resonance imaging scans, and extensive cognitive testing. In addition, blood samples are collected for various laboratory measurements and blood biomarker analysis and cerebrospinal fluid samples are collected from a subset of participants based on additional voluntary informed consent. To evaluate the predictive value of the early neuroimaging findings, neuropsychological evaluation and blood biomarker measurements will be repeated after a 4-year follow-up period.& nbsp;Discussion:& nbsp;Results of the ASIC-E4 project will bridge the gap related to limited knowledge of the synaptic and inflammatory changes and their association with each other and A beta in "at-risk " individuals. Thorough in vivo characterization of the biomarker profiles in this population will produce valuable information for diagnostic purposes and future drug development, where the field has already started to look beyond A beta.
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- Golla, Sandeep S V, et al.
(författare)
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Parametric Binding Images of the TSPO Ligand 18F-DPA-714.
- 2016
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Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 57:10, s. 1543-1547
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Tidskriftsartikel (refereegranskat)abstract
- (18)F-labeled N,N-diethyl-2-(2-[4-(2-fluoroethoxy)phenyl]-5,7-dimethylpyrazolo[1,5-α]pyrimidine-3-yl)acetamide (DPA-714) is a radioligand for the 18-kDa translocator protein. The purpose of the present study was to identify the best method for generating quantitative parametric images of (18)F-DPA-714 binding.METHODS: Ninety-minute dynamic (18)F-DPA-714 PET scans with full arterial sampling from 6 healthy subjects and 9 Alzheimer disease (AD) patients were used. Plasma-input-based Logan graphical analysis and spectral analysis were used to generate parametric volume of distribution (VT) images. Five versions of Ichise, reference Logan, and 2 basis function implementations (receptor parametric mapping and simplified reference tissue model 2 [SRTM2]) of SRTM, all using gray matter cerebellum as the reference region, were applied to generate nondisplaceable binding potential (BPND) images.RESULTS: Plasma-input Logan analysis (r(2) = 0.99; slope, 0.88) and spectral analysis (r(2) = 0.99, slope, 0.93) generated estimates of VT that correlated well with values obtained using nonlinear regression. BPND values generated using SRTM2 (r(2) = 0.83; slope, 0.95) and reference Logan analysis (r(2) = 0.88; slope, 1.01) correlated well with nonlinear regression-based estimates.CONCLUSION: Both Logan analysis and spectral analysis can be used to obtain quantitatively accurate VT images of (18)F-DPA-714. In addition, SRTM2 and reference Logan analysis can provide accurate BPND images. These parametric images could be used for voxel-based comparisons.
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| 7. |
- Golla, Sandeep S V, et al.
(författare)
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Quantification of [18F]DPA-714 binding in the human brain : initial studies in healthy controls and Alzheimer's disease patients
- 2015
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 0271-678X .- 1559-7016. ; 35:5, s. 766-772
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Tidskriftsartikel (refereegranskat)abstract
- Fluorine-18 labelled N,N-diethyl-2-(2-[4-(2-fluoroethoxy)phenyl]-5,7-dimethylpyrazolo[1,5-α]pyrimidine-3-yl)acetamide ([(18)F]DPA-714) binds to the 18-kDa translocator protein (TSPO) with high affinity. The aim of this initial methodological study was to develop a plasma input tracer kinetic model for quantification of [(18)F]DPA-714 binding in healthy subjects and Alzheimer's disease (AD) patients, and to provide a preliminary assessment whether there is a disease-related signal. Ten AD patients and six healthy subjects underwent a dynamic positron emission tomography (PET) study along with arterial sampling and a scan protocol of 150 minutes after administration of 250 ± 10 MBq [(18)F]DPA-714. The model that provided the best fits to tissue time activity curves (TACs) was selected based on Akaike Information Criterion and F-test. The reversible two tissue compartment plasma input model with blood volume parameter was the preferred model for quantification of [(18)F]DPA-714 kinetics, irrespective of scan duration, volume of interest, and underlying volume of distribution (VT). Simplified reference tissue model (SRTM)-derived binding potential (BPND) using cerebellar gray matter as reference tissue correlated well with plasma input-based distribution volume ratio (DVR). These data suggest that [(18)F]DPA-714 cannot be used for separating individual AD patients from healthy subjects, but further studies including TSPO binding status are needed to substantiate these findings.
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