Publications
469 results found
Wilson H, Niccolini F, Hirschbichler S, et al., 2017, In vivo tau and amyloid pathology in Corticobasal Degeneration (CBD), 28th International Symposium on Cerebral Blood Flow, Metabolism and Function / 13th International Conference on Quantification of Brain Function with PET, Publisher: SAGE PUBLICATIONS INC, Pages: 92-92, ISSN: 0271-678X
Kobayashi M, Jiang T, Telu S, et al., 2017, (11)C-DPA-713 has much greater specific binding to translocator protein 18 kDa (TSPO) in human brain than (11)C-( R)-PK11195, Journal of Cerebral Blood Flow and Metabolism, Vol: 38, Pages: 393-403, ISSN: 1559-7016
Positron emission tomography (PET) radioligands for translocator protein 18 kDa (TSPO) are widely used to measure neuroinflammation, but controversy exists whether second-generation radioligands are superior to the prototypical agent (11)C-( R)-PK11195 in human imaging. This study sought to quantitatively measure the "signal to background" ratio (assessed as binding potential ( BPND)) of (11)C-( R)-PK11195 compared to one of the most promising second-generation radioligands, (11)C-DPA-713. Healthy subjects had dynamic PET scans and arterial blood measurements of radioligand after injection of either (11)C-( R)-PK11195 (16 subjects) or (11)C-DPA-713 (22 subjects). To measure the amount of specific binding, a subset of these subjects was scanned after administration of the TSPO blocking drug XBD173 (30-90 mg PO). (11)C-DPA-713 showed a significant sensitivity to genotype in brain, whereas (11)C-( R)-PK11195 did not. Lassen occupancy plot analysis revealed that the specific binding of (11)C-DPA-713 was much greater than that of (11)C-( R)-PK11195. The BPND in high-affinity binders was about 10-fold higher for (11)C-DPA-713 (7.3) than for (11)C-( R)-PK11195 (0.75). Although the high specific binding of (11)C-DPA-713 suggests it is an ideal ligand to measure TSPO, we also found that its distribution volume increased over time, consistent with the accumulation of radiometabolites in brain.
Chen DL, Cheriyan J, Chilvers ER, et al., 2017, Quantification of lung PET images: challenges and opportunities., Journal of Nuclear Medicine, Vol: 58, Pages: 201-207, ISSN: 1535-5667
Millions of people are affected by respiratory diseases, leading to a significant health burden globally. Because of the current insufficient knowledge of the underlying mechanisms that lead to the development and progression of respiratory diseases, treatment options remain limited. To overcome this limitation and understand the associated molecular changes, noninvasive imaging techniques such as PET and SPECT have been explored for biomarker development, with (18)F-FDG PET imaging being the most studied. The quantification of pulmonary molecular imaging data remains challenging because of variations in tissue, air, blood, and water fractions within the lungs. The proportions of these components further differ depending on the lung disease. Therefore, different quantification approaches have been proposed to address these variabilities. However, no standardized approach has been developed to date. This article reviews the data evaluating (18)F-FDG PET quantification approaches in lung diseases, focusing on methods to account for variations in lung components and the interpretation of the derived parameters. The diseases reviewed include acute respiratory distress syndrome, chronic obstructive pulmonary disease, and interstitial lung diseases such as idiopathic pulmonary fibrosis. Based on review of prior literature, ongoing research, and discussions among the authors, suggested considerations are presented to assist with the interpretation of the derived parameters from these approaches and the design of future studies.
Kalk NJ, Guo Q, Owen D, et al., 2017, Decreased hippocampal translocator protein (18 kDa) expression in alcohol dependence: a [(11)C]PBR28 PET study, Translational Psychiatry, Vol: 7, ISSN: 2158-3188
Repeated withdrawal from alcohol is clinically associated with progressive cognitive impairment. Microglial activation occurring during pre-clinical models of alcohol withdrawal is associated with learning deficits. We investigated whether there was microglial activation in recently detoxified alcohol-dependent patients (ADP), using [(11)C]PBR28 positron emission tomography (PET), selective for the 18kDa translocator protein (TSPO) highly expressed in activated microglia and astrocytes. We investigated the relationship between microglial activation and cognitive performance. Twenty healthy control (HC) subjects (45±13; M:F 14:6) and nine ADP (45±6, M:F 9:0) were evaluated. Dynamic PET data were acquired for 90 min following an injection of 331±15 MBq [(11)C]PBR28. Regional volumes of distribution (VT) for regions of interest (ROIs) identified a priori were estimated using a two-tissue compartmental model with metabolite-corrected arterial plasma input function. ADP had an ~20% lower [(11)C]PBR28 VT, in the hippocampus (F(1,24) 5.694; P=0.025), but no difference in VT in other ROIs. Hippocampal [(11)C]PBR28 VT was positively correlated with verbal memory performance in a combined group of HC and ADP (r=0.720, P<0.001), an effect seen in HC alone (r=0.738; P=0.001) but not in ADP. We did not find evidence for increased microglial activation in ADP, as seen pre-clinically. Instead, our findings suggest lower glial density or an altered activation state with lower TSPO expression. The correlation between verbal memory and [(11)C]PBR28 VT, raises the possibility that abnormalities of glial function may contribute to cognitive impairment in ADP.
Datta G, Violante IR, Scott G, et al., 2016, Translocator positron-emission tomography and magnetic resonance spectroscopic imaging of brain glial cell activation in multiple sclerosis., Multiple Sclerosis, Vol: 23, Pages: 1469-1478, ISSN: 1352-4585
BACKGROUND: Multiple sclerosis (MS) is characterised by a diffuse inflammatory response mediated by microglia and astrocytes. Brain translocator protein (TSPO) positron-emission tomography (PET) and [myo-inositol] magnetic resonance spectroscopy (MRS) were used together to assess this. OBJECTIVE: To explore the in vivo relationships between MRS and PET [(11)C]PBR28 in MS over a range of brain inflammatory burden. METHODS: A total of 23 patients were studied. TSPO PET imaging with [(11)C]PBR28, single voxel MRS and conventional magnetic resonance imaging (MRI) sequences were undertaken. Disability was assessed by Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Functional Composite (MSFC). RESULTS: [(11)C]PBR28 uptake and [ myo-inositol] were not associated. When the whole cohort was stratified by higher [(11)C]PBR28 inflammatory burden, [ myo-inositol] was positively correlated to [(11)C]PBR28 uptake (Spearman's ρ = 0.685, p = 0.014). Moderate correlations were found between [(11)C]PBR28 uptake and both MRS creatine normalised N-acetyl aspartate (NAA) concentration and grey matter volume. MSFC was correlated with grey matter volume (ρ = 0.535, p = 0.009). There were no associations between other imaging or clinical measures. CONCLUSION: MRS [ myo-inositol] and PET [(11)C]PBR28 measure independent inflammatory processes which may be more commonly found together with more severe inflammatory disease. Microglial activation measured by [(11)C]PBR28 uptake was associated with loss of neuronal integrity and grey matter atrophy.
Dimber R, Guo Q, Bishop C, et al., 2016, Evidence of brain inflammation in patients with Human T Lymphotropic Virus type 1 associated myelopathy (HAM): A pilot, multi-modal imaging study using [11C] PBR28 PET, MR T1w and DWI, Journal of Nuclear Medicine, Vol: 57, Pages: 1905-1912, ISSN: 1535-5667
HAM is a chronic debilitating neuroinflammatory disease with a predilection for the thoraciccord. Tissue damage is attributed to the cellular immune response to HTLV-1 infectedlymphocytes. Using a specific 18KDa Translocator Protein ligand, [11C] PBR28, T1-weightedand Diffusion Weighted magnetic resonance imaging, the brains of HTLV-1 infected patients,with and without HAM but no clinical evidence of brain involvement, were examined.Methods: Five subjects with HAM and two HTLV-1 asymptomatic carriers (AC) werestudied. All underwent clinical neurological assessment including cognitive function andobjective measures of gait, quantification of HTLV-1 proviral load in peripheral bloodmononuclear cells and HLA DR expression on circulating CD8+ lymphocytes. [11C] PBR28PET and MRI were performed on the same day. [11C]PBR28 PET total volume of distribution(VT) and distribution volume ratio (DVR) were estimated using 2-tissue compartmentmodelling. MRI data was processed using tools from the FMRIB Software Library (FSL) toestimate mean diffusivity (MD) and grey matter (GM) fraction changes. The results werecompared with data from age matched healthy volunteers.Results: Across the whole brain the VT for the subjects with HAM (5.44±0.84) wassignificantly greater than those of AC (3.44±0.80). The DVR of thalamus in patients withsevere and moderate HAM were higher compared to the healthy volunteers suggestingincreased TSPO binding (z>4.72). Subjects with more severe myelopathy and with high DRexpression on CD8+ lymphocytes had increased DVR and MD (near-significant correlationfound for the right thalamus MD: p=0.06). On the T1-weighted MRI scans, the GM fractionof the brain stem was reduced in all HTLV1-infected patients compared to controls(p<0.001), whilst the thalamus GM fraction was decreased in patients with HAM andcorrelated with the disease severity. There was no correlation between neurocognitivefunction and these markers of CNS inflammation.3Conclusio
Colasanti A, Guo Q, Jacobson P, et al., 2016, Effect of Glucocorticoids on Tspo Expression in Nonhuman Primate Brain Evaluated Using Positron Emission Tomography, Publisher: NATURE PUBLISHING GROUP, Pages: S166-S167, ISSN: 0893-133X
Rabiner E, Erritzoe D, Searle G, et al., 2016, Amphetamine Induced Endogenous Serotonin Release in the Human Brain: A Pet Study With [11C] cimbi-36, Publisher: NATURE PUBLISHING GROUP, Pages: S202-S203, ISSN: 0893-133X
Gunn RN, Rabiner EA, 2016, Imaging in central nervous system drug discovery, Seminars in Nuclear Medicine, Vol: 47, Pages: 89-98, ISSN: 1558-4623
The discovery and development of central nervous system (CNS) drugs is an extremely challenging process requiring large resources, timelines, and associated costs. The high risk of failure leads to high levels of risk. Over the past couple of decades PET imaging has become a central component of the CNS drug-development process, enabling decision-making in phase I studies, where early discharge of risk provides increased confidence to progress a candidate to more costly later phase testing at the right dose level or alternatively to kill a compound through failure to meet key criteria. The so called "3 pillars" of drug survival, namely; tissue exposure, target engagement, and pharmacologic activity, are particularly well suited for evaluation by PET imaging. This review introduces the process of CNS drug development before considering how PET imaging of the "3 pillars" has advanced to provide valuable tools for decision-making on the critical path of CNS drug development. Finally, we review the advances in PET science of biomarker development and analysis that enable sophisticated drug-development studies in man.
Mick I, Ramos C, Myers J, et al., 2016, Evidence for GABA-A receptor dysregulation in gambling disorder: correlation with impulsivity., Addiction Biology, Vol: 22, Pages: 1601-1609, ISSN: 1369-1600
Background: As a behavioral addiction, gambling disorder (GD) provides an opportunity to characterize addictive processes without the potentially confounding effects of chronic excessive drug and alcohol exposure. Impulsivity is an established precursor to such addictive behaviours and GD is associated with greater impulsivity. There is also evidence of GABAergic dysregulation in substance addiction and in impulsivity. Methods: This study therefore investigated GABAA receptor availability in 15 individuals with GD and 19 healthy volunteers (HV) using [11C]Ro15-4513, a relatively selective α5 benzodiazepine receptor PET tracer and its relationship with impulsivity. Results: We found significantly higher [11C]Ro15-4513 total distribution volume (VT) in the right hippocampus in the GD group compared with HV. We found higher levels of The ‘Negative Urgency’ construct of impulsivity in GD and these were positively associated with higher [11C]Ro15-4513 VT in the amygdala in the GD group; no such significant correlations were evident in the HV group. Conclusions: These results contrast with reduced binding of GABAergic PET ligands described previously in alcohol and opiate addiction and add to growing evidence for distinctions in the neuropharmacology between substance and behavioral addictions. These results provide the first characterization of GABAA receptors in GD with [11C]Ro15-4513 PET and show greater α5 receptor availability and positive correlations with trait impulsivity. This GABAergic dysregulation is potential target for treatment.
Russo E, Khan S, Janisch R, et al., 2016, Role of 18F-fluorodeoxyglucose Positron Emission Tomography in the Monitoring of Inflammatory Activity in Crohn's Disease., Inflammatory Bowel Diseases, ISSN: 1536-4844
Background: 18Fluorine-fluorodeoxyglucose positron emission tomography (18F-FDG PET) has recently attracted interest for the measurement ofdisease activity in Crohn’s disease (CD). The aim of this study was to assess the utility of FDG-PET as a marker of progression of inflammatory activityand its response to treatment in patients with CD.Methods: Twenty-two patients with active CD were recruited prospectively to undergo FDG-PET scanning at 2 time points. All 22 index scans were used toassess sensitivity and specificity against a reference standard magnetic resonance imaging measure. Correlations with clinicopathological markers of severity(Harvey-Bradshaw Index, C-reactive protein, and calprotectin) were also performed. Of note, 17/22 patients participated in the longitudinal component andunderwent scanning before and 12 weeks after the initiation of anti–tumor necrosis factor alpha therapy. Patients were subcategorized on the basis ofa clinically significant response, and responsiveness of the PET measures was assessed using previously described indices. Of note, 5/22 patients took partin the test–retest component of the study and underwent scanning twice within a target interval of 1 week, to assess the reproducibility of the PET measures.Results: The sensitivity and specificity of 18F-FDG PET were 88% and 70%, respectively. Standardized uptake value (SUV)-related PET measurescorrelated significantly both with C-reactive protein and Harvey-Bradshaw Index in cross-sectional and longitudinal analyses. (G)SUVMAX and (G)SUVMEANdemonstrated favorable responsiveness and reliability characteristics (responsiveness ratio of Guyatt .0.80 and % variability ,20%) compared with volumedependentFDG-PET measures. A proportion of the FDG signal (10%–30%) was found to originate from the lumen of diseased segments.Conclusions: 18F-FDG PET may be useful for longitudinal monitoring of inflammatory activity in CD.
Wilson H, Niccolini F, Haider S, et al., 2016, Loss of extra-striatal phosphodiesterase 10A expression in early premanifest Huntington's disease gene carriers., Journal of the Neurological Sciences, Vol: 368, Pages: 243-248, ISSN: 0022-510X
Huntington's disease (HD) is a monogenic neurodegenerative disorder with an underlying pathology involving the toxic effect of mutant huntingtin protein primarily in striatal and cortical neurons. Phosphodiesterase 10A (PDE10A) regulates intracellular signalling cascades, thus having a key role in promoting neuronal survival. Using positron emission tomography (PET) with [(11)C]IMA107, we investigated the in vivo extra-striatal expression of PDE10A in 12 early premanifest HD gene carriers. Image processing and kinetic modelling was performed using MIAKAT™. Parametric images of [(11)C]IMA107 non-displaceable binding potential (BPND) were generated from the dynamic [(11)C]IMA107 scans using the simplified reference tissue model with the cerebellum as the reference tissue for nonspecific binding. We set a threshold criterion for meaningful quantification of [(11)C]IMA107 BPND at 0.30 in healthy control data; regions meeting this criterion were designated as regions of interest (ROIs). MRI-based volumetric analysis showed no atrophy in ROIs. We found significant differences in mean ROIs [(11)C]IMA107 BPND between HD gene carriers and healthy controls. HD gene carriers had significant loss of PDE10A within the insular cortex and occipital fusiform gyrus compared to healthy controls. Insula and occipital fusiform gyrus are important brain areas for the regulation of cognitive and limbic function that is impaired in HD. Our findings suggest that dysregulation of PDE10A-mediated intracellular signalling could be an early phenomenon in the course of HD with relevance also for extra-striatal brain areas.
Myers JFM, Comley RA, Gunn RN, 2016, Quantification of [11C]Ro15-4513 GABAAα5 specific binding and regional selectivity in humans, Journal of Cerebral Blood Flow and Metabolism, Vol: 37, Pages: 2137-2148, ISSN: 1559-7016
[11C]Ro15-4513 has been introduced as a PET radioligand to image the GABAAα5 receptorsubtype thought to be important in learning, memory and addiction. However, the in vivoselectivity of the ligand remains unknown and a full assessment of different analysisapproaches has yet to be performed. Using human heterologous competition data, with[11C]Ro15-4513 and the highly selective GABAAα5 selective negative allosteric modulatorBasmisanil (RG1662), we quantify the GABAAα5 selectivity of [11C]Ro15-4513, assess thevalidity of reference tissues and evaluate the performance of four different kinetic analysismethods. The results show that [11C]Ro15-4513 has high but not complete selectivity forGABAAα5, with α5 representing around 60-70% of the specific binding in α5 rich regions.Competition data indicate that the cerebellum and pons are essentially devoid of α5 signaland might be used as reference regions under certain conditions. Off-target non-selectivebinding to other GABAA subtypes means that the choice of analysis method and theinterpretation of outcome measures must be considered carefully. We discuss the merits oftwo tissue compartmental model analyses to derive both and , band-pass spectralanalysis for estimation of and the simplifified reference tissue model for estimation of BPnd.
Myers J, Comley R, Gunn R, 2016, Quantification of [11C]Ro15-4513 GABAAα5 specific binding and regional selectivity in humans, JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, Vol: 36, Pages: 623-624, ISSN: 0271-678X
Colasanti A, Guo Q, Giannetti P, et al., 2016, Neuroinflammation and genesis of affective symptoms in multiple sclerosis: integrating evidence from TSPO PET and resting state FMRI, Bipolar Disorders, Vol: 18, Pages: 84-84, ISSN: 1398-5647
Feeney C, Scott G, Raffel J, et al., 2016, Kinetic analysis of the translocator protein positron emission tomography ligand [18F]GE-180 in the human brain, European Journal of Nuclear Medicine and Molecular Imaging, Vol: 43, Pages: 2201-2210, ISSN: 1619-7089
PURPOSE: PET can image neuroinflammation by targeting the translocator protein (TSPO), which is upregulated in activated microglia. The high nonspecific binding of the first-generation TSPO radioligand [(11)C]PK-11195 limits accurate quantification. [(18)F]GE-180, a novel TSPO ligand, displays superior binding to [(11)C]PK-11195 in vitro. Our objectives were to: (1) evaluate tracer characteristics of [(18)F]GE-180 in the brains of healthy human subjects; and (2) investigate whether the TSPO Ala147Thr polymorphism influences outcome measures. METHODS: Ten volunteers (five high-affinity binders, HABs, and five mixed-affinity binders, MABs) underwent a dynamic PET scan with arterial sampling after injection of [(18)F]GE-180. Kinetic modelling of time-activity curves with one-tissue and two-tissue compartment models and Logan graphical analysis was applied to the data. The primary outcome measure was the total volume of distribution (V T) across various regions of interest (ROIs). Secondary outcome measures were the standardized uptake values (SUV), the distribution volume and SUV ratios estimated using a pseudoreference region. RESULTS: The two-tissue compartment model was the best model. The average regional delivery rate constant (K 1) was 0.01 mL cm(-3) min(-1) indicating low extraction across the blood-brain barrier (1 %). The estimated median V T across all ROIs was also low, ranging from 0.16 mL cm(-3) in the striatum to 0.38 mL cm(-3) in the thalamus. There were no significant differences in V T between HABs and MABs across all ROIs. CONCLUSION: A reversible two-tissue compartment model fitted the data well and determined that the tracer has a low first-pass extraction (approximately 1 %) and low V T estimates in healthy individuals. There was no observable dependency on the rs6971 polymorphism as compared to other second-generation TSPO PET tracers. Investigation of [(18)F]GE-180 in populations with neuroinflammatory disease is nee
Wilson H, Niccolini F, Haider S, et al., 2016, Loss of extra-striatal phosphodiesterase 10A expression in early premanifest Huntington's disease gene carriers, 20th International Congress of Parkinson's Disease and Movement Disorders, Publisher: WILEY-BLACKWELL, Pages: S353-S354, ISSN: 0885-3185
Searle GE, Coello C, Gunn RN, 2016, REALISING THE BINDING POTENTIAL DIRECTLY AND INDIRECTLY, 27th International Symposium on Cerebral Blood Flow, Metabolism and Function / 12th International Conference on Quantification of Brain Function with PET, Publisher: SAGE PUBLICATIONS INC, Pages: 17-18, ISSN: 0271-678X
Guo Q, Owen DR, Kalk NJ, et al., 2016, INVESTIGATION OF THE VARIABILITY OF THE TSPO RADIOLIGAND [11C]PBR28 IN HUMAN BRAIN, 27th International Symposium on Cerebral Blood Flow, Metabolism and Function / 12th International Conference on Quantification of Brain Function with PET, Publisher: SAGE PUBLICATIONS INC, Pages: 76-77, ISSN: 0271-678X
Whittington A, Iturria-Medina Y, Evans A, et al., 2016, MODEL TO DESCRIBE THE SPATIOTEMPORAL DISTRIBUTION OF MISFOLDED PROTEINS IN ALZHEIMER'S DISEASE, 27th International Symposium on Cerebral Blood Flow, Metabolism and Function / 12th International Conference on Quantification of Brain Function with PET, Publisher: SAGE PUBLICATIONS INC, Pages: 79-80, ISSN: 0271-678X
Hannestad J, Seibyl J, Marek K, et al., 2016, DIFFERENT RATES OF DOPAMINE TRANSPORTER LOSS IN PARKINSON'S DISEASE AS MEASURED WITH [123I]beta-CIT AND [123I]FP-CIT SPECT, JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, Vol: 36, Pages: 186-187, ISSN: 0271-678X
Newbould RD, Bishop C, Searle G, et al., 2016, Mapping brain response to an adenosine A2A antagonist using [11c]sch442416 pet and arterial spin labeling (ASL) cerebral blood flow (CBF) perfusion magnetic resonance imaging, 27th International Symposium on Cerebral Blood Flow, Metabolism and Function / 12th International Conference on Quantification of Brain Function with PET, Publisher: SAGE Publications, Pages: 391-392, ISSN: 1559-7016
Scott G, Gunn RN, Matthews PM, et al., 2016, Minocycline reduces microglial activation after traumatic brain injury measured using [11C]-PBR28 positron emission tomography, International Brain Injury Association’s Eleventh World Congress on Brain Injury, Publisher: Taylor & Francis, Pages: 686-687, ISSN: 1362-301X
Coello C, Fisk M, Wilson F, et al., 2016, Quantitative analysis of dynamic 18F-FDG in lungs of HV and COPD subjects, Publisher: SOC NUCLEAR MEDICINE INC, ISSN: 0161-5505
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Gunn R, Coello C, Searle G, 2016, Molecular Imaging And Kinetic Analysis Toolbox (MIAKAT) - A Quantitative Software Package for the Analysis of PET Neuroimaging Data, Publisher: SOC NUCLEAR MEDICINE INC, ISSN: 0161-5505
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Whittington A, Sharp D, Gunn R, 2016, Spatiotemporal distribution of β-amyloid in Alzheimer's Disease results from heterogeneous regional carrying capacities, Publisher: SOC NUCLEAR MEDICINE INC, ISSN: 0161-5505
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Gallezot J-D, Guo Q, Gunn R, et al., 2016, Evaluation and correction of biases induced by the use of automated whole-blood measurements in TSPO PET studies using 11C-PBR28, Publisher: SOC NUCLEAR MEDICINE INC, ISSN: 0161-5505
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Mick I, Myers J, Ramos AC, et al., 2016, Blunted Endogenous Opioid Release Following an Oral Amphetamine Challenge in Pathological Gamblers, 3rd International Conference on Behavioral Addictions, Publisher: Akadémiai Kiadó, Pages: 30-30, ISSN: 2063-5303
Vera JH, Guo Q, Cole JH, et al., 2016, Neuroinflammation in treated HIV-positive individuals: A TSPO PET study, Neurology, Vol: 86, Pages: 1425-1432, ISSN: 1526-632X
OBJECTIVE: To explore the effects of microglial activation on brain function and structure, and its relationship with peripheral inflammatory markers, in treated, HIV-positive individuals, using in vivo [(11)C]PBR28 PET (to measure the 18 kDa translocator protein [TSPO]). METHODS: Cognitively healthy HIV-positive individuals on suppressive antiretroviral therapy and HIV-negative individuals (controls) underwent brain [(11)C]PBR28 PET and MRI. HIV-positive patients completed neuropsychological testing and CSF testing for chemokines. The concentration of bacterial ribosomal 16sDNA in plasma was measured as a marker of microbial translocation. RESULTS: HIV-positive individuals showed global increases in TSPO expression compared to controls (corrected p < 0.01), with significant regional increases in the parietal (p = 0.001) and occipital (p = 0.046) lobes and in the globus pallidus (p = 0.035). TSPO binding in the hippocampus, amygdala, and thalamus were associated with poorer global cognitive performance in tasks assessing verbal and visual memory (p < 0.05). Increased TSPO binding was associated with increased brain white matter diffusion MRI mean diffusivity in HIV-positive individuals, a lower CD4/CD8 ratio, and both high pretreatment HIV RNA and plasma concentration ribosomal 16s DNA (p < 0.05). CONCLUSIONS: Cognitively healthy HIV-positive individuals show evidence for a chronically activated brain innate immune response and elevated blood markers of microbial translocation despite effective control of plasma viremia. Increased brain inflammation is associated with poorer cognitive performance and white matter microstructural pathology, suggesting a possible role in cognitive impairments found in some HIV-positive patients despite effective treatment.
Marques TR, Natesan S, Niccolini F, et al., 2016, Phosphodiesterase 10A in Schizophrenia: A PET Study Using [(11)C]IMA107., American Journal of Psychiatry, Vol: 173, Pages: 714-721, ISSN: 1535-7228
OBJECTIVE: Phosphodiesterase 10A (PDE10A) is an enzyme present in striatal medium spiny neurons that degrades the intracellular second messengers triggered by dopamine signaling. The pharmaceutical industry has considerable interest in PDE10A inhibitors because they have been shown to have an antipsychotic-like effect in animal models. However, the status of PDE10A in schizophrenia is unknown. Using a newly developed and validated radioligand, [(11)C]IMA107, the authors report the first in vivo assessment of PDE10A brain expression in patients with schizophrenia. METHOD: The authors compared PDE10A availability in the brains of 12 patients with chronic schizophrenia and 12 matched healthy comparison subjects using [(11)C]IMA107 positron emission tomography (PET). Regional estimates of the binding potential (BPND) of [(11)C]IMA107 were generated from dynamic PET scans using the simplified reference tissue model with the cerebellum as the reference tissue for nonspecific binding. RESULTS: There was no significant difference in [(11)C]IMA107 BPND between schizophrenia patients and comparison subjects in any of the brain regions studied (thalamus, caudate, putamen, nucleus accumbens, globus pallidus, and substantia nigra). There was also no significant correlation between [(11)C]IMA107 BPND and the severity of psychotic symptoms or antipsychotic dosage. CONCLUSIONS: Patients with schizophrenia have normal availability of PDE10A in brain regions thought to be involved in the pathophysiology of this disorder. The findings do not support the proposal of an altered PDE10A availability in schizophrenia. The implication of this finding for future drug development is discussed.
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