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Article ; Online: Cerebral acetylcholinesterase activity is not decreased in MS patients with cognitive impairment.

Virta, Jere R / Laatu, Sari / Parkkola, Riitta / Oikonen, Vesa / Rinne, Juha O / Ruutiainen, Juhani

Multiple sclerosis (Houndmills, Basingstoke, England)

2011 Volume 17, Issue 8, Page(s) 931–938

Abstract: Background: Neuropsychological studies have extensively described the presence of cognitive dysfunction in MS patients. One possible pharmacological treatment of the impairment could be based on acetylcholinesterase inhibitors (AChEIs), which have shown ...

Abstract	Background: Neuropsychological studies have extensively described the presence of cognitive dysfunction in MS patients. One possible pharmacological treatment of the impairment could be based on acetylcholinesterase inhibitors (AChEIs), which have shown efficacy in alleviating cognitive impairment in many other disorders. The findings on the efficacy of AChEI medication in MS associated cognitive symptoms are preliminary and no studies concerning cerebral acetylcholinesterase (AChE) activity in these patients have been published. Objective: The objective of the study was to examine cerebral AChE activity in cognitively deteriorated MS patients. Cerebral AChE activity of 10 MS patients with secondary progressive disease and marked cognitive impairment, and 10 healthy controls, was studied with positron emission tomography using tracer (11)C-MP4A. Methods: The cognitive profile of the patients was assessed with CERAD (Consortium to Establish a Registry for Alzheimer's Disease). Results: No differences in cortical AChE activity between MS patients and controls were seen. Conclusions: In the patient group regional AChE activities had inverse correlations with Word learning and MMSE (Mini-Mental State Examination) scores. In the group of cognitively deteriorated MS patients no change in cerebral AChE activity, compared with controls, was observed, but within the patient group more pronounced cognitive symptoms were associated with higher cerebral AChE activity.
MeSH term(s)	Acetylcholinesterase/metabolism ; Adult ; Cerebral Cortex/diagnostic imaging ; Cerebral Cortex/enzymology ; Cognition Disorders/diagnostic imaging ; Cognition Disorders/enzymology ; Cognition Disorders/etiology ; Female ; Humans ; Image Processing, Computer-Assisted ; Male ; Middle Aged ; Multiple Sclerosis/complications ; Multiple Sclerosis/diagnostic imaging ; Multiple Sclerosis/enzymology ; Neuropsychological Tests ; Positron-Emission Tomography
Chemical Substances	Acetylcholinesterase (EC 3.1.1.7)
Language	English
Publishing date	2011-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1290669-4
ISSN	1477-0970 ; 1352-4585
ISSN (online)	1477-0970
ISSN	1352-4585
DOI	10.1177/1352458511399613
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Zs.A 4428: Show issues

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Article ; Online: Adenosine A2A receptors in secondary progressive multiple sclerosis: a [(11)C]TMSX brain PET study.

Rissanen, Eero / Virta, Jere R / Paavilainen, Teemu / Tuisku, Jouni / Helin, Semi / Luoto, Pauliina / Parkkola, Riitta / Rinne, Juha O / Airas, Laura

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism

2013 Volume 33, Issue 9, Page(s) 1394–1401

Abstract: In this study, positron emission tomography (PET) imaging with a radioligand to adenosine A2A receptors (A2AR)-a potent regulator of inflammation-was used to gain insight into the molecular alterations in normal-appearing white matter (NAWM) and gray ... ...

Abstract	In this study, positron emission tomography (PET) imaging with a radioligand to adenosine A2A receptors (A2AR)-a potent regulator of inflammation-was used to gain insight into the molecular alterations in normal-appearing white matter (NAWM) and gray matter (GM) in secondary progressive multiple sclerosis (SPMS). Normal-appearing white matter and GM, despite seeming normal in conventional magnetic resonance imaging (MRI), are important loci of widespread inflammation, neuronal damage, and source of progressive disability in multiple sclerosis (MS). Dynamic PET imaging using A2AR-specific [(11)C]TMSX and brain MRI with diffusion tensor imaging were performed to eight SPMS patients and seven healthy controls. Distribution volumes (VT) of [(11)C]TMSX were analyzed from 13 regions of interest using Logan plot with arterial plasma input. The SPMS patients had significantly increased [(11)C]TMSX-VT in NAWM compared with controls (mean (s.d.): 0.55 (±0.08) vs. 0.45 (±0.05); P=0.036). Both the increased VT and the decreased fractional anisotropy (FA) in NAWM were associated with higher expanded disability status scale (EDSS) scores (P=0.030 and P=0.012, respectively), whereas the T2-lesion load of SPMS patients did not correlate with EDSS. This study shows, that A2ARs are increased in the brain of SPMS patients, and that [(11)C]TMSX-PET provides a novel approach to learn about central nervous system pathology in SPMS in vivo.
MeSH term(s)	Adult ; Aged ; Cerebral Cortex/diagnostic imaging ; Cerebral Cortex/metabolism ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Multiple Sclerosis/diagnostic imaging ; Multiple Sclerosis/metabolism ; Positron-Emission Tomography ; Radiography ; Radioligand Assay ; Receptor, Adenosine A2A/metabolism
Chemical Substances	Receptor, Adenosine A2A
Language	English
Publishing date	2013-05-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604628-9
ISSN	1559-7016 ; 0271-678X
ISSN (online)	1559-7016
ISSN	0271-678X
DOI	10.1038/jcbfm.2013.85
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Zs.A 1663: Show issues

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Article: 1-11C-methyl-4-piperidinyl-N-butyrate radiation dosimetry in humans by dynamic organ-specific evaluation.

Virta, Jere R / Tolvanen, Tuula / Någren, Kjell / Brück, Anna / Roivainen, Anne / Rinne, Juha O

Journal of nuclear medicine : official publication, Society of Nuclear Medicine

2008 Volume 49, Issue 3, Page(s) 347–353

Abstract: Unlabelled: Deficits of cholinergic neurotransmission contribute to various neurologic and psychiatric conditions. The neurotransmitter acetylcholine is hydrolyzed in the synaptic clefts by 2 enzymes, acetylcholinesterase (AChE) and ... ...

Abstract	Unlabelled: Deficits of cholinergic neurotransmission contribute to various neurologic and psychiatric conditions. The neurotransmitter acetylcholine is hydrolyzed in the synaptic clefts by 2 enzymes, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). 1-[(11)C]-Methyl-4-piperidinyl-N-butyrate ((11)C-MP4B) is a radioligand for the assessment study of BuChE activity in human brain with PET. In the present study the radiation-absorbed doses of the (11)C-MP4B were estimated in humans according to the guidelines of the International Commission on Radiological Protection. Two different data acquisition protocols-dynamic organ-specific evaluation (DOSE) and whole-body scanning-were compared. Both methods are widely used for evaluation of radiation burden of (11)C-labeled PET tracers. Methods: Fixed-bed PET on the upper neck, thorax, abdomen, or pelvic region was performed on 7 healthy subjects after injection of 707 +/- 34 MBq (mean +/- SD) of (11)C-MP4B. Brain input was derived from our previous studies on 18 healthy control subjects and 10 patients with Alzheimer's disease. Regions of interest were drawn on transverse images of all visible organs. Radiation dose estimates were calculated from organ residence times using the MIRDOSE3 software. Urine samples were collected after imaging to estimate tracer extraction. To compare the estimates for absorbed doses between the whole-body scan approach and the DOSE method, we simulated whole-body data acquisition methods used in (11)C dosimetry studies with our fixed-bed data. Results: The organs with the highest radiation-absorbed doses were the liver, urinary bladder, kidneys (renal cortex), upper large intestine, trabecular bone, salivary glands, and heart wall. Up to 60% of the injected dose was excreted via the urinary pathway, and the clearance was relatively rapid, as 30% of the radioactivity was excreted within 60 min after injection. With a 2-h voiding interval the effective dose was 4.2 microSv/MBq. Conclusion: (11)C-MP4B causes less radiation burden than previously studied (11)C-labeled PET tracers. No intolerably high absorbed doses were observed in critical organs. With 740 MBq of injected radioactivity, the radiation burden is equivalent to 3.11 mSv. This would allow multiple PET examinations per year to be performed on the same subject. The DOSE method and the simulated whole-body imaging approach produced similar results.
MeSH term(s)	Adult ; Body Burden ; Butyrates/analysis ; Butyrates/pharmacokinetics ; Humans ; Male ; Metabolic Clearance Rate ; Models, Biological ; Organ Specificity ; Piperidines/analysis ; Piperidines/pharmacokinetics ; Radiation Dosage ; Radiopharmaceuticals/analysis ; Radiopharmaceuticals/pharmacokinetics ; Relative Biological Effectiveness ; Tissue Distribution ; Whole-Body Counting
Chemical Substances	Butyrates ; Piperidines ; Radiopharmaceuticals ; methyl-4-piperidinyl n-butyrate
Language	English
Publishing date	2008-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80272-4
ISSN	1535-5667 ; 0161-5505 ; 0097-9058 ; 0022-3123
ISSN (online)	1535-5667
ISSN	0161-5505 ; 0097-9058 ; 0022-3123
DOI	10.2967/jnumed.107.047233
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Zs.A 114: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 328: Show issues

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Article ; Online: Parametric Binding Images of the TSPO Ligand 18F-DPA-714.

Golla, Sandeep S V / Boellaard, Ronald / Oikonen, Vesa / Hoffmann, Anja / van Berckel, Bart N M / Windhorst, Albert D / Virta, Jere / Te Beek, Erik T / Groeneveld, Geert Jan / Haaparanta-Solin, Merja / Luoto, Pauliina / Savisto, Nina / Solin, Olof / Valencia, Ray / Thiele, Andrea / Eriksson, Jonas / Schuit, Robert C / Lammertsma, Adriaan A / Rinne, Juha O

Journal of nuclear medicine : official publication, Society of Nuclear Medicine

2016 Volume 57, Issue 10, Page(s) 1543–1547

Abstract: 18: Methods: Ninety-minute dynamic : Results: Plasma-input Logan analysis (r: Conclusion ...

Abstract	18 Methods: Ninety-minute dynamic Results: Plasma-input Logan analysis (r Conclusion: Both Logan analysis and spectral analysis can be used to obtain quantitatively accurate V
MeSH term(s)	Adult ; Alzheimer Disease/diagnostic imaging ; Alzheimer Disease/metabolism ; Case-Control Studies ; Female ; Fluorine Radioisotopes ; Humans ; Ligands ; Male ; Middle Aged ; Positron-Emission Tomography ; Protein Binding ; Pyrazoles/metabolism ; Pyrimidines/metabolism ; Receptors, GABA/metabolism ; Statistics as Topic
Chemical Substances	Fluorine Radioisotopes ; Ligands ; N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo(1,5-a)pyrimidin-3-yl)acetamide ; Pyrazoles ; Pyrimidines ; Receptors, GABA ; TSPO protein, human
Language	English
Publishing date	2016-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	80272-4
ISSN	1535-5667 ; 0097-9058 ; 0161-5505 ; 0022-3123
ISSN (online)	1535-5667
ISSN	0097-9058 ; 0161-5505 ; 0022-3123
DOI	10.2967/jnumed.116.173013
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Zs.A 114: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 328: Show issues

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Article ; Online: Cholinergic activity correlates with reserve proxies in Alzheimer's disease.

Garibotto, Valentina / Tettamanti, Marco / Marcone, Alessandra / Florea, Ioana / Panzacchi, Andrea / Moresco, Rosamaria / Virta, Jere R / Rinne, Juha / Cappa, Stefano F / Perani, Daniela

Neurobiology of aging

2013 Volume 34, Issue 11, Page(s) 2694.e13–8

Abstract: The clinical expression of Alzheimer's disease (AD) occurs as neuropathology exceeds the brain "reserve capacity." A possible association between the cholinergic system and reserve is suggested by preclinical observations that the cholinergic system ... ...

Abstract	The clinical expression of Alzheimer's disease (AD) occurs as neuropathology exceeds the brain "reserve capacity." A possible association between the cholinergic system and reserve is suggested by preclinical observations that the cholinergic system allows cortical plasticity and by clinical observations of variable responses to cholinergic treatments depending on the patient's educational level. The aim of this study was to investigate the association of reserve proxies, that is, education and occupation, with acetylcholinesterase (AChE) activity, measured voxelwise by [(11)C]-MP4A and positron emission tomography (PET), in 9 healthy controls (HC), 7 patients with early probable AD, and 9 subjects with mild cognitive impairment (MCI) at the time of PET imaging, who progressed to AD at follow-up (prodromal AD). The analysis of prodromal and early AD showed positive correlations between education and AChE activity in the hippocampus, bilaterally, and between occupation and AChE activity in the right posterior cingulate gyrus. The significant correlation between AChE activity in structures belonging to the memory network and reserve proxies suggests that the brain reserve in AD is associated with a preserved/stimulated cholinergic neurotransmission.
MeSH term(s)	Acetates ; Acetylcholine/metabolism ; Aged ; Aged, 80 and over ; Alzheimer Disease/diagnostic imaging ; Alzheimer Disease/physiopathology ; Carbon Isotopes ; Cognitive Dysfunction/diagnostic imaging ; Cognitive Dysfunction/physiopathology ; Cognitive Reserve/physiology ; Educational Status ; Employment ; Female ; Fluorodeoxyglucose F18 ; Humans ; Male ; Mental Status Schedule ; Middle Aged ; Piperidines ; Positron-Emission Tomography ; Radiography ; Statistics, Nonparametric ; Tomography Scanners, X-Ray Computed
Chemical Substances	Acetates ; Carbon Isotopes ; N-methyl-4-piperidyl acetate ; Piperidines ; Fluorodeoxyglucose F18 (0Z5B2CJX4D) ; Acetylcholine (N9YNS0M02X)
Language	English
Publishing date	2013-11
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604505-4
ISSN	1558-1497 ; 0197-4580
ISSN (online)	1558-1497
ISSN	0197-4580
DOI	10.1016/j.neurobiolaging.2013.05.020
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Zs.A 1685: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 10: Show issues

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Article ; Online: Test-retest reliability of (11)C-ORM-13070 in PET imaging of α2C-adrenoceptors in vivo in the human brain.

Lehto, Jussi / Virta, Jere R / Oikonen, Vesa / Roivainen, Anne / Luoto, Pauliina / Arponen, Eveliina / Helin, Semi / Hietamäki, Johanna / Holopainen, Aila / Kailajärvi, Marita / Peltonen, Juha M / Rouru, Juha / Sallinen, Jukka / Virtanen, Kirsi / Volanen, Iina / Scheinin, Mika / Rinne, Juha O

European journal of nuclear medicine and molecular imaging

2014 Volume 42, Issue 1, Page(s) 120–127

Abstract: Purpose: α2C-Adrenoceptors share inhibitory presynaptic functions with the more abundant α2A-adrenoceptor subtype, but they also have widespread postsynaptic modulatory functions in the brain. Research on the noradrenergic system of the human brain has ... ...

Abstract	Purpose: α2C-Adrenoceptors share inhibitory presynaptic functions with the more abundant α2A-adrenoceptor subtype, but they also have widespread postsynaptic modulatory functions in the brain. Research on the noradrenergic system of the human brain has been hampered by the lack of suitable PET tracers targeted to the α2-adrenoceptor subtypes. Methods: PET imaging with the specific α2C-adrenoceptor antagonist tracer [(11)C]ORM-13070 was performed twice in six healthy male subjects to investigate the test-retest reliability of tracer binding. Results: The bound/free ratio of tracer uptake relative to nonspecific uptake into the cerebellum during the time interval of 5 - 30 min was most prominent in the dorsal striatum: 0.77 in the putamen and 0.58 in the caudate nucleus. Absolute test-retest variability in bound/free ratios of tracer ranged from 4.3 % in the putamen to 29 % in the hippocampus. Variability was also <10 % in the caudate nucleus and thalamus. Intraclass correlation coefficients (ICC) ranged from 0.50 in the hippocampus to 0.89 in the thalamus (ICC >0.70 was also reached in the caudate nucleus, putamen, lateral frontal cortex and parietal cortex). The pattern of [(11)C]ORM-13070 binding, as determined by PET, was in good agreement with receptor density results previously derived from post-mortem autoradiography. PET data analysis results obtained with a compartmental model fit, the simplified reference tissue model and a graphical reference tissue analysis method were convergent with the tissue ratio method. Conclusion: The results of this study support the use of [(11)C]ORM-13070 PET in the quantitative assessment of α2C-adrenoceptors in the human brain in vivo. Reliable assessment of specific tracer binding in the dorsal striatum is possible with the help of reference tissue ratios.
MeSH term(s)	Adult ; Brain/diagnostic imaging ; Dioxanes/pharmacokinetics ; Humans ; Male ; Piperazines/pharmacokinetics ; Positron-Emission Tomography ; Radiopharmaceuticals/pharmacokinetics ; Receptors, Adrenergic, alpha-2/metabolism ; Reproducibility of Results ; Tissue Distribution
Chemical Substances	1-(1-(2,3-dihydrobenzo(1,4)dioxin-2-yl)methyl)-4-(3-methoxymethylpyridin-2-yl)piperazine ; Dioxanes ; Piperazines ; Radiopharmaceuticals ; Receptors, Adrenergic, alpha-2
Language	English
Publishing date	2014-09-09
Publishing country	Germany
Document type	Evaluation Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	8236-3
ISSN	1619-7089 ; 0340-6997 ; 1619-7070
ISSN (online)	1619-7089
ISSN	0340-6997 ; 1619-7070
DOI	10.1007/s00259-014-2899-z
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Zs.A 1227: Show issues

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Article ; Online: [11C]-MP4A PET cholinergic measurements in amnestic mild cognitive impairment, probable Alzheimer's disease, and dementia with Lewy bodies: a Bayesian method and voxel-based analysis.

Marcone, Alessandra / Garibotto, Valentina / Moresco, Rosa Maria / Florea, Ioana / Panzacchi, Andrea / Carpinelli, Assunta / Virta, Jere R / Tettamanti, Marco / Borroni, Barbara / Padovani, Alessandro / Bertoldo, Alessandra / Herholz, Karl / Rinne, Juha O / Cappa, Stefano Francesco / Perani, Daniela

Journal of Alzheimer's disease : JAD

2012 Volume 31, Issue 2, Page(s) 387–399

Abstract: Non-invasive approaches for positron emission tomography (PET) parametric imaging of acetylcholinesterase (AChE) activity have been developed and applied to the investigation of dementia, mainly Alzheimer's disease (AD), but also dementia with Lewy ... ...

Abstract	Non-invasive approaches for positron emission tomography (PET) parametric imaging of acetylcholinesterase (AChE) activity have been developed and applied to the investigation of dementia, mainly Alzheimer's disease (AD), but also dementia with Lewy bodies (DLB), not including, however, patients in the early disease stage. The few cholinergic PET studies on mild cognitive impairment (MCI) did not provide clinical follow-up. One limitation of the methods used so far is the relatively low sensitivity in measuring subcortical or deep cortical structures, which might represent specific disease markers. Here we assessed AChE activity with [11C]-MP4A and PET by a maximum a posteriori Bayesian method (MAPB) based on a 2-tissue compartment-3-rate-constant reference region model. 30 subjects were included: 10 multi-domain amnestic MCI (aMCI) with a follow up of 2 years, 7 probable AD (pAD), 4 DLB subjects, and 9 healthy controls. Regions of interest and voxel-based statistical parametric mapping analyses revealed significant and widespread AChE reductions in several cortical regions and in the hippocampus in all pAD subjects and aMCI subjects who progressed to AD (converters). Noteworthy, hippocampal AChE activity correlated significantly with long-term verbal and non-verbal memory in both aMCI converters and pAD. The pattern was more heterogeneous in early DLB patients, with only 2 out of 4 cases showing a severe or intermediate reduction of AChE activity. The comparable AChE reductions in pAD and aMCI converters indicate the presence of a widespread impairment of the cholinergic system already in the MCI phase. A more variable degree of cholinergic dysfunction is present in early DLB.
MeSH term(s)	Acetates ; Acetylcholinesterase/metabolism ; Aged ; Aged, 80 and over ; Amnesia/diagnostic imaging ; Amnesia/metabolism ; Amnesia/psychology ; Bayes Theorem ; Carbon Radioisotopes ; Cognitive Dysfunction/diagnostic imaging ; Cognitive Dysfunction/metabolism ; Cognitive Dysfunction/psychology ; Female ; Humans ; Lewy Body Disease/diagnostic imaging ; Lewy Body Disease/metabolism ; Lewy Body Disease/psychology ; Male ; Middle Aged ; Piperidines ; Positron-Emission Tomography
Chemical Substances	Acetates ; Carbon Radioisotopes ; N-methyl-4-piperidyl acetate ; Piperidines ; Acetylcholinesterase (EC 3.1.1.7)
Language	English
Publishing date	2012
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1440127-7
ISSN	1875-8908 ; 1387-2877
ISSN (online)	1875-8908
ISSN	1387-2877
DOI	10.3233/JAD-2012-111748
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Zs.A 6084: Show issues

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Article ; Online: Cerebral oxygen and glucose metabolism in patients with mitochondrial m.3243A>G mutation.

Lindroos, Markus M / Borra, Ronald J / Parkkola, Riitta / Virtanen, Sami M / Lepomäki, Virva / Bucci, Marco / Virta, Jere R / Rinne, Juha O / Nuutila, Pirjo / Majamaa, Kari

Brain : a journal of neurology

2009 Volume 132, Issue Pt 12, Page(s) 3274–3284

Abstract: The m.3243A>G mutation is the most common pathogenic mutation in mitochondrial DNA. It leads to defective oxidative phosphorylation, decreased oxygen consumption and increased glucose utilization and lactate production in vitro. However, oxygen and ... ...

Abstract	The m.3243A>G mutation is the most common pathogenic mutation in mitochondrial DNA. It leads to defective oxidative phosphorylation, decreased oxygen consumption and increased glucose utilization and lactate production in vitro. However, oxygen and glucose metabolism has not been studied in the brain of patients harbouring the m.3243A>G mutation. Therefore, 14 patients with the m.3243A>G mutation, not experiencing acute stroke-like episodes and 14 age-matched controls underwent positron emission tomography using 2-[(18)F]fluoro-2-deoxyglucose, [(15)O]H(2)O and [(15)O]O(2) as the tracers during normoglycaemia. The metabolic rate of oxygen and glucose were determined using a quantitative region of interest analysis. Metabolites in unaffected periventricular tissue were measured using magnetic resonance spectroscopy. We found that the cerebral metabolic rate of oxygen was decreased by 26% (range 18%-29%) in the grey as well as the white matter of patients with the m.3243A>G mutation. A decrease in the metabolic rate of glucose was found with predilection to the posterior part of the brain. No major changes were detected in cerebral blood flow or the number of white matter lesions. Our results show that the m.3243A>G mutation leads to a global decrease in oxygen consumption in the grey matter including areas where no other signs of disease were present.
MeSH term(s)	Adult ; Brain/metabolism ; Brain/physiopathology ; Brain Diseases, Metabolic/diagnostic imaging ; Brain Diseases, Metabolic/genetics ; Brain Diseases, Metabolic/metabolism ; Cerebral Cortex/metabolism ; Cerebral Cortex/physiopathology ; DNA Mutational Analysis ; Energy Metabolism/genetics ; Female ; Genetic Predisposition to Disease/genetics ; Genetic Testing ; Glucose/metabolism ; Humans ; Hypoxia, Brain/diagnostic imaging ; Hypoxia, Brain/genetics ; Hypoxia, Brain/metabolism ; Magnetic Resonance Spectroscopy ; Male ; Middle Aged ; Mitochondrial Diseases/diagnostic imaging ; Mitochondrial Diseases/genetics ; Mitochondrial Diseases/metabolism ; Mitochondrial Proteins/genetics ; Mutation/genetics ; Oxygen Consumption/genetics ; Positron-Emission Tomography
Chemical Substances	Mitochondrial Proteins ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2009-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80072-7
ISSN	1460-2156 ; 0006-8950
ISSN (online)	1460-2156
ISSN	0006-8950
DOI	10.1093/brain/awp259
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Article ; Online: Quantification of [18F]DPA-714 binding in the human brain: initial studies in healthy controls and Alzheimer's disease patients.

Golla, Sandeep S V / Boellaard, Ronald / Oikonen, Vesa / Hoffmann, Anja / van Berckel, Bart N M / Windhorst, Albert D / Virta, Jere / Haaparanta-Solin, Merja / Luoto, Pauliina / Savisto, Nina / Solin, Olof / Valencia, Ray / Thiele, Andrea / Eriksson, Jonas / Schuit, Robert C / Lammertsma, Adriaan A / Rinne, Juha O

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism

2015 Volume 35, Issue 5, Page(s) 766–772

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 ...

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.
MeSH term(s)	Aged ; Aged, 80 and over ; Alzheimer Disease/diagnostic imaging ; Alzheimer Disease/metabolism ; Female ; Fluorine Radioisotopes/administration & dosage ; Fluorine Radioisotopes/pharmacokinetics ; Humans ; Kinetics ; Male ; Middle Aged ; Models, Biological ; Positron-Emission Tomography ; Pyrazoles/administration & dosage ; Pyrazoles/adverse effects ; Pyrimidines/administration & dosage ; Pyrimidines/adverse effects ; Radiography ; Receptors, GABA/metabolism ; Time Factors
Chemical Substances	Fluorine Radioisotopes ; N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo(1,5-a)pyrimidin-3-yl)acetamide ; Pyrazoles ; Pyrimidines ; Receptors, GABA ; TSPO protein, human
Language	English
Publishing date	2015-05
Publishing country	United States
Document type	Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	604628-9
ISSN	1559-7016 ; 0271-678X
ISSN (online)	1559-7016
ISSN	0271-678X
DOI	10.1038/jcbfm.2014.261
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Human biodistribution and radiation dosimetry of 11C-(R)-PK11195, the prototypic PET ligand to image inflammation.

Hirvonen, Jussi / Roivainen, Anne / Virta, Jere / Helin, Semi / Någren, Kjell / Rinne, Juha O

European journal of nuclear medicine and molecular imaging

2009 Volume 37, Issue 3, Page(s) 606–612

Abstract: Purpose: The positron emission tomography (PET) radiotracer (11)C-(R)-PK11195 allows the in vivo ... with (11)C-(R)-PK11195 in humans is not known. To examine this, we performed dynamic whole-body imaging ... with PET and (11)C-(R)-PK11195 in healthy humans.: Methods: Five healthy male volunteers were scanned ...

Abstract	Purpose: The positron emission tomography (PET) radiotracer (11)C-(R)-PK11195 allows the in vivo imaging in humans of the translocator protein 18 kDa (TSPO), previously called peripheral benzodiazepine receptor (PBR), a marker of inflammation. Despite its widespread use, the radiation burden associated with (11)C-(R)-PK11195 in humans is not known. To examine this, we performed dynamic whole-body imaging with PET and (11)C-(R)-PK11195 in healthy humans. Methods: Five healthy male volunteers were scanned with PET and (11)C-(R)-PK11195, using a dynamic whole-body imaging protocol. An organ-specific method was used to measure accumulated radioactivity in source organs, and residence times were calculated as areas under the curve of time-activity curves expressed as percentage of injected radioactivity. Residence times were used as input for OLINDA/EXM 1.0 software to model the equivalent organ doses and the effective dose for the 70-kg man. Results: After intravenous injection of (11)C-(R)-PK11195, radioactivity accumulated in organs rich in TSPO as well as routes of excretion: the hepatobiliary system and the urine. The mean effective dose was 4.8 microSv/MBq according to International Commission on Radiological Protection (ICRP) Publication 60 and 5.1 microSv/MBq according to ICRP Publication 103, and the highest equivalent organ doses were observed in the kidneys (14.0 microSv/MBq), spleen (12.5 microSv/MBq) and small intestine (12.2 microSv/MBq). Conclusion: Imaging of TSPO with PET using (11)C-(R)-PK11195 is associated with modest radiation exposure, similar in magnitude to most other (11)C-labelled PET tracers, suggesting feasibility of (11)C-(R)-PK11195 imaging in clinical human studies involving multiple scans in the same subjects per year.
MeSH term(s)	Amides/administration & dosage ; Amides/pharmacokinetics ; Humans ; Inflammation/diagnostic imaging ; Injections, Intravenous ; Isoquinolines/administration & dosage ; Isoquinolines/pharmacokinetics ; Ligands ; Male ; Metabolic Clearance Rate ; Positron-Emission Tomography ; Radiometry ; Tissue Distribution ; Young Adult
Chemical Substances	(R)-(11C)1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide ; Amides ; Isoquinolines ; Ligands
Language	English
Publishing date	2009-10-28
Publishing country	Germany
Document type	Clinical Trial ; Journal Article
ZDB-ID	8236-3
ISSN	1619-7089 ; 0340-6997 ; 1619-7070
ISSN (online)	1619-7089
ISSN	0340-6997 ; 1619-7070
DOI	10.1007/s00259-009-1298-3
Database	MEDical Literature Analysis and Retrieval System OnLINE

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