Age and disease related changes in the translocator protein (TSPO) system in the human brain: Positron emission tomography measurements with [11C]vinpocetine (584 views)
Neuroimage (ISSN: 1053-8119, 1053-8119linking), 2011 Jun 1; 56(3): 1111-1121.
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Paper type: Journal Article,
Impact factor: 5.895, 5-year impact factor: 6.608
Url: http://www.scopus.com/inward/record.url?eid=2-s2.0-79955468959&partnerID=40&md5=7b4aa75e00a2285bfe27f3e7601c35e8
Keywords: [11c]vinpocetine, Ageing, Alzheimer, S Disease (ad), Brain Uptake, Imaging Biomarker, Inhomogeneity Analysis, Microglia, Molecular Imaging, Peripheral Benzodiazepine Receptor (pbr), Positron Emission Tomography (pet), Translocator Protein (tspo), Carrier Protein, Radiopharmaceutical Agent, Unclassified Drug, Vinpocetine C 11, Adult, Age Distribution, Article, Binding Affinity, Brain Region, Drug Protein Binding, Drug Targeting, Drug Uptake, Human, Human Experiment, Nerve Cell Stimulation, Normal Human, Priority Journal, Spectral Sensitivity, Upregulation, 80 And Over, Alzheimer Disease, Data Interpretation, Statistical, Female, Image Processing, Computer-Assisted, Isotope Labeling, Middle Aged, Positron-Emission Tomography, Gaba, Vinca Alkaloids, [11c] Vinpocetine,
Affiliations:
*** IBB - CNR ***
Karolinska Institutet, Department of Clinical Neuroscience, Centrum for Psychiatry Research, S-17176 Stockholm, Sweden
Chemical Works of Gedeon Richter Plc, Budapest, H-1103, Hungary
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Neuroimage (ISSN: 1053-8119, 1053-8119linking), 2011 Jun 1; 56(3): 1111-1121.
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Paper type: Journal Article,
Impact factor: 5.895, 5-year impact factor: 6.608
Url: http://www.scopus.com/inward/record.url?eid=2-s2.0-79955468959&partnerID=40&md5=7b4aa75e00a2285bfe27f3e7601c35e8
Keywords: [11c]vinpocetine, Ageing, Alzheimer, S Disease (ad), Brain Uptake, Imaging Biomarker, Inhomogeneity Analysis, Microglia, Molecular Imaging, Peripheral Benzodiazepine Receptor (pbr), Positron Emission Tomography (pet), Translocator Protein (tspo), Carrier Protein, Radiopharmaceutical Agent, Unclassified Drug, Vinpocetine C 11, Adult, Age Distribution, Article, Binding Affinity, Brain Region, Drug Protein Binding, Drug Targeting, Drug Uptake, Human, Human Experiment, Nerve Cell Stimulation, Normal Human, Priority Journal, Spectral Sensitivity, Upregulation, 80 And Over, Alzheimer Disease, Data Interpretation, Statistical, Female, Image Processing, Computer-Assisted, Isotope Labeling, Middle Aged, Positron-Emission Tomography, Gaba, Vinca Alkaloids, [11c] Vinpocetine,
Affiliations:
*** IBB - CNR ***
Karolinska Institutet, Department of Clinical Neuroscience, Centrum for Psychiatry Research, S-17176 Stockholm, Sweden
Chemical Works of Gedeon Richter Plc, Budapest, H-1103, Hungary
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Age and disease related changes in the translocator protein (TSPO) system in the human brain: Positron emission tomography measurements with [11C]vinpocetine
Backgrounds and purpose: The main objectives of the present study were (i) to measure density changes of activated microglia and the peripheral benzodiazepine receptor/translocator protein (TSPO) system during normal ageing in the human brain with positron emission tomography (PET) using the TSPO molecular imaging biomarker [11C]vinpocetine and (ii) to compare the level and pattern of TSPO in Alzheimer (AD) patients with age matched healthy subjects, in order to assess the biomarker's usefulness as a diagnostic imaging marker in normal (ageing) and pathological (AD) up-regulation of microglia. Methods and subjects: PET measurements were made in healthy volunteers, aged between 25 and 78years, and AD patients, aged between 67 and 82years, using [11C]vinpocetine as the tracer. Global and regional quantitative parameters of tracer uptake and binding, including time activity curves (TAC) of standard uptake values (%SUV), binding affinity parameters, intensity spectrum and homogeneity of the uptake distribution were measured and analysed. Results: Both %SUV and binding values increased with age linearly in the whole brain and in all brain regions. There were no significant differences between the %SUV values of the AD patients and age matched control subjects. There were, however, significant differences in %SUV values in a large number of brain regions between young subjects and old subjects, as well as young subjects and AD patients. The intensity spectrum analysis and homogeneity analysis of the voxel data show that the homogeneity of the %SUV values decreases with ageing and during the disease, whereas the centre of the intensity spectrum is shifted to higher %SUV values. These data indicate an inhomogeneous up-regulation of the TSPO system during ageing and AD. These changes were significant between the group of young subjects and old subjects, as well as young subjects and AD patients, but not between old subjects and AD patients. Conclusions: The present data indicate that [11C]vinpocetine may serve as a molecular imaging biomarker of the activity of the TSPO system and, consequently, of the up-regulation of microglia during ageing and in neuroinflammatory diseases. However, the global and regional brain %SUV values between AD patients and age matched controls are not different from each other. The disease specific changes, measured with [11C]vinpocetine in AD, are significantly different from those measured in age matched controls only if the inhomogeneities in the uptake pattern are explored with advanced mathematical techniques. For this reason, PET studies using [11C]vinpocetine, as molecular imaging biomarker, can efficiently visualise the activation of microglia and the up-regulation of TSPO during ageing and in diseased brains with the help of an appropriate inhomogeneity analysis of the radioligand's brain uptake pattern. © 2011 Elsevier Inc.
Backgrounds and purpose: The main objectives of the present study were (i) to measure density changes of activated microglia and the peripheral benzodiazepine receptor/translocator protein (TSPO) system during normal ageing in the human brain with positron emission tomography (PET) using the TSPO molecular imaging biomarker [11C]vinpocetine and (ii) to compare the level and pattern of TSPO in Alzheimer (AD) patients with age matched healthy subjects, in order to assess the biomarker's usefulness as a diagnostic imaging marker in normal (ageing) and pathological (AD) up-regulation of microglia. Methods and subjects: PET measurements were made in healthy volunteers, aged between 25 and 78years, and AD patients, aged between 67 and 82years, using [11C]vinpocetine as the tracer. Global and regional quantitative parameters of tracer uptake and binding, including time activity curves (TAC) of standard uptake values (%SUV), binding affinity parameters, intensity spectrum and homogeneity of the uptake distribution were measured and analysed. Results: Both %SUV and binding values increased with age linearly in the whole brain and in all brain regions. There were no significant differences between the %SUV values of the AD patients and age matched control subjects. There were, however, significant differences in %SUV values in a large number of brain regions between young subjects and old subjects, as well as young subjects and AD patients. The intensity spectrum analysis and homogeneity analysis of the voxel data show that the homogeneity of the %SUV values decreases with ageing and during the disease, whereas the centre of the intensity spectrum is shifted to higher %SUV values. These data indicate an inhomogeneous up-regulation of the TSPO system during ageing and AD. These changes were significant between the group of young subjects and old subjects, as well as young subjects and AD patients, but not between old subjects and AD patients. Conclusions: The present data indicate that [11C]vinpocetine may serve as a molecular imaging biomarker of the activity of the TSPO system and, consequently, of the up-regulation of microglia during ageing and in neuroinflammatory diseases. However, the global and regional brain %SUV values between AD patients and age matched controls are not different from each other. The disease specific changes, measured with [11C]vinpocetine in AD, are significantly different from those measured in age matched controls only if the inhomogeneities in the uptake pattern are explored with advanced mathematical techniques. For this reason, PET studies using [11C]vinpocetine, as molecular imaging biomarker, can efficiently visualise the activation of microglia and the up-regulation of TSPO during ageing and in diseased brains with the help of an appropriate inhomogeneity analysis of the radioligand's brain uptake pattern. © 2011 Elsevier Inc.
Age and disease related changes in the translocator protein (TSPO) system in the human brain: Positron emission tomography measurements with [11C]vinpocetine
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Age and disease related changes in the translocator protein (TSPO) system in the human brain: Positron emission tomography measurements with [11C]vinpocetine
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De Rosa V, Iommelli F, Monti M, Mainolfi CG, Fonti R, Del Vecchio S
* Early 18F-FDG uptake as a reliable imaging biomarker of T790M-mediated resistance but not MET amplification in non-small cell lung cancer treated with EGFR tyrosine kinase inhibitors (315 views)
Ejnmmi Res, 2016 Dec; 6(1): 74-74.
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De Rosa V, Iommelli F, Monti M, Mainolfi C, Fonti R, Del Vecchio S
* Early 18F-FDG uptake as a reliable imaging biomarker of T790M-mediated resistance but not MET amplification in NSCLC (370 views)
Eur J Nucl Med (ISSN: 1619-7070, 1619-7089, 1619-7070print), 2015 Oct; 42: N/D-N/D.
Impact Factor: 5.537
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* Early 18F-FDG uptake as a reliable imaging biomarker of T790M-mediated resistance but not MET amplification in non-small cell lung cancer treated with EGFR tyrosine kinase inhibitors (315 views)
Ejnmmi Res, 2016 Dec; 6(1): 74-74.
Impact Factor: 1.761
View Export to BibTeX Export to EndNote
De Rosa V, Iommelli F, Monti M, Mainolfi C, Fonti R, Del Vecchio S
* Early 18F-FDG uptake as a reliable imaging biomarker of T790M-mediated resistance but not MET amplification in NSCLC (370 views)
Eur J Nucl Med (ISSN: 1619-7070, 1619-7089, 1619-7070print), 2015 Oct; 42: N/D-N/D.
Impact Factor: 5.537
View Export to BibTeX Export to EndNote
2 Records (1 excluding Abstracts).
Total impact factor: 7.298 (1.761 excluding Abstracts).
Total 5 year impact factor: 5.145 (0 excluding Abstracts).
Total impact factor: 7.298 (1.761 excluding Abstracts).
Total 5 year impact factor: 5.145 (0 excluding Abstracts).
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