Mapping neuroinflammation in frontotemporal dementia with molecular PET imaging

Recent findings have led to a renewed interest and support for an active role of inflammation in neurodegenerative dementias and related neurologic disorders. Detection of neuroinflammation in vivo throughout the course of neurodegenerative diseases is of great clinical interest. Studies have shown that microglia activation (an indicator of neuroinflammation) may present at early stages of frontotemporal dementia (FTD), but the role of neuroinflammation in the pathogenesis of FTD is largely unknown. The first-generation translocator protein (TSPO) ligand ([11C]-PK11195) has been used to detect microglia activation in FTD, and the second-generation TSPO ligands have imaged neuroinflammation in vivo with improved pharmacokinetic properties. This paper reviews related literature and technical issues on mapping neuroinflammation in FTD with positron-emission tomography (PET) imaging. Early detection of neuroinflammation in FTD may identify new tools for diagnosis, novel treatment targets, and means to monitor therapeutic efficacy. More studies are needed to image and track neuroinflammation in FTD. It is anticipated that the advances of TSPO PET imaging will overcome technical difficulties, and molecular imaging of neuroinflammation will aid in the characterization of neuroinflammation in FTD. Such knowledge has the potential to shed light on the poorly understood pathogenesis of FTD and related dementias, and provide imaging markers to guide the development and assessment of new therapies.

[1]  Hans Förstl,et al.  Frontotemporal lobar degeneration: current perspectives , 2014, Neuropsychiatric disease and treatment.

[2]  Masanori Ichise,et al.  Correlation between FEPPA uptake and microglia activation in 6-OHDA injured rat brain , 2010, NeuroImage.

[3]  C. van Broeckhoven,et al.  Mechanisms of Granulin Deficiency: Lessons from Cellular and Animal Models , 2012, Molecular Neurobiology.

[4]  N. Volkow,et al.  Distribution Volume Ratios without Blood Sampling from Graphical Analysis of PET Data , 1996, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[5]  A. Slachevsky,et al.  Human platelets tau: a potential peripheral marker for Alzheimer's disease. , 2011, Journal of Alzheimer's disease : JAD.

[6]  Nick C Fox,et al.  Conversion of amyloid positive and negative MCI to AD over 3 years , 2009, Neurology.

[7]  C. V. van Duijn,et al.  Medical and environmental risk factors for sporadic frontotemporal dementia: a retrospective case–control study , 2003, Journal of neurology, neurosurgery, and psychiatry.

[8]  M. Kassiou,et al.  Could 18 F-DPA-714 PET imaging be interesting to use in the early post-stroke period? , 2014, EJNMMI Research.

[9]  Alan A. Wilson,et al.  Voxel-Based Imaging of Translocator Protein 18Kda (TSPO) in High-Resolution PET , 2013, Journal of Cerebral Blood Flow and Metabolism.

[10]  S. Gauthier,et al.  Tracking neuroinflammation in Alzheimer’s disease: the role of positron emission tomography imaging , 2014, Journal of Neuroinflammation.

[11]  A. Reynolds,et al.  Initial evaluation in healthy humans of [18F]DPA-714, a potential PET biomarker for neuroinflammation. , 2012, Nuclear medicine and biology.

[12]  J. Hodges,et al.  Survival in frontotemporal dementia , 2003, Neurology.

[13]  R. Maccioni,et al.  Neuroinflammation in the pathogenesis of Alzheimer’s disease. A rational framework for the search of novel therapeutic approaches , 2014, Front. Cell. Neurosci..

[14]  R. Boisgard,et al.  The Translocator Protein Radioligand 18F-DPA-714 Monitors Antitumor Effect of Erufosine in a Rat 9L Intracranial Glioma Model , 2013, The Journal of Nuclear Medicine.

[15]  Robert B. Innis,et al.  Mixed-Affinity Binding in Humans with 18-kDa Translocator Protein Ligands , 2011, The Journal of Nuclear Medicine.

[16]  Robert B. Innis,et al.  Kinetic analysis in healthy humans of a novel positron emission tomography radioligand to image the peripheral benzodiazepine receptor, a potential biomarker for inflammation , 2008, NeuroImage.

[17]  B. Gulyás,et al.  Functional neuroimaging in multiple sclerosis with radiolabelled glia markers: Preliminary comparative PET studies with [11C]vinpocetine and [11C]PK11195 in patients , 2008, Journal of the Neurological Sciences.

[18]  F. Yasuno,et al.  Increased binding of peripheral benzodiazepine receptor in mild cognitive impairment–dementia converters measured by positron emission tomography with [11C]DAA1106 , 2012, Psychiatry Research: Neuroimaging.

[19]  J. Crispino,et al.  Molecular Pathogenesis of Genetic and Inherited Diseases Progranulin Is a Chemoattractant for Microglia and Stimulates Their Endocytic Activity , 2010 .

[20]  W. Slikker,et al.  Protective Effects of Acetyl L-Carnitine on Inhalation Anesthetic-Induced Neuronal Damage in the Nonhuman Primate , 2013 .

[21]  M. Sastre,et al.  Modulation of inflammation in transgenic models of Alzheimer’s disease , 2014, Journal of Neuroinflammation.

[22]  Alessandra Bertoldo,et al.  Kinetic Modeling without Accounting for the Vascular Component Impairs the Quantification of [11C]PBR28 Brain PET Data , 2014, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[23]  A. Lammertsma,et al.  Simplified Reference Tissue Model for PET Receptor Studies , 1996, NeuroImage.

[24]  Annelaure Damont,et al.  Comparative Evaluation of the Translocator Protein Radioligands 11C-DPA-713, 18F-DPA-714, and 11C-PK11195 in a Rat Model of Acute Neuroinflammation , 2009, Journal of Nuclear Medicine.

[25]  [Initial symptoms, survival and causes of death in 115 patients with frontotemporal lobar degeneration]. , 2007, Fortschritte der Neurologie-Psychiatrie.

[26]  R. Petersen,et al.  neurodegeneration : evidence for association of the p . R 47 H variant with frontotemporal dementia and Parkinson ¿ s disease Permalink , 2013 .

[27]  I. Mackenzie,et al.  Advances in understanding the molecular basis of frontotemporal dementia , 2012, Nature Reviews Neurology.

[28]  Sylvain Houle,et al.  Quantitation of Translocator Protein Binding in Human Brain with the Novel Radioligand [18F]-FEPPA and Positron Emission Tomography , 2011, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[29]  F. Turkheimer,et al.  Reference and target region modeling of [11C]-(R)-PK11195 brain studies. , 2007, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[30]  C. Cotman,et al.  Bcl-2 family protein behavior in frontotemporal dementia implies vascular involvement , 2001, Neurology.

[31]  D. Geschwind,et al.  TDP-43 frontotemporal lobar degeneration and autoimmune disease , 2013, Journal of Neurology, Neurosurgery & Psychiatry.

[32]  F. Yasuno,et al.  In vivo detection of neuropathologic changes in presymptomatic MAPT mutation carriers: a PET and MRI study. , 2010, Parkinsonism & related disorders.

[33]  Jeih-San Liow,et al.  Linearized Reference Tissue Parametric Imaging Methods: Application to [11C]DASB Positron Emission Tomography Studies of the Serotonin Transporter in Human Brain , 2003, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[34]  F. LaFerla,et al.  Lipopolysaccharide-Induced Inflammation Exacerbates Tau Pathology by a Cyclin-Dependent Kinase 5-Mediated Pathway in a Transgenic Model of Alzheimer's Disease , 2005, The Journal of Neuroscience.

[35]  Frederik Barkhof,et al.  Microglial activation in Alzheimer's disease: an (R)-[11C]PK11195 positron emission tomography study , 2013, Neurobiology of Aging.

[36]  G. Sedvall,et al.  Quantitative analysis of D2 dopamine receptor binding in the living human brain by PET. , 1986, Science.

[37]  R. Boisgard,et al.  [18F]DPA-714 as a biomarker for positron emission tomography imaging of rheumatoid arthritis in an animal model , 2014, Arthritis Research & Therapy.

[38]  Marco Prinz,et al.  Microglia and brain macrophages in the molecular age: from origin to neuropsychiatric disease , 2014, Nature Reviews Neuroscience.

[39]  A. Singleton,et al.  Using exome sequencing to reveal mutations in TREM2 presenting as a frontotemporal dementia-like syndrome without bone involvement. , 2012, JAMA neurology.

[40]  W. Slikker,et al.  MicroPET/CT Imaging of [18F]-FEPPA in the Nonhuman Primate: A Potential Biomarker of Pathogenic Processes Associated with Anesthetic-Induced Neurotoxicity , 2012 .

[41]  Zsolt Cselényi,et al.  A comparison of recent parametric neuroreceptor mapping approaches based on measurements with the high affinity PET radioligands [11C]FLB 457 and [11C]WAY 100635 , 2006, NeuroImage.

[42]  Yota Fujimura,et al.  Quantification of Translocator Protein (18 kDa) in the Human Brain with PET and a Novel Radioligand, 18F-PBR06 , 2009, Journal of Nuclear Medicine.

[43]  Raymond Scott Turner,et al.  Temporoparietal hypometabolism in frontotemporal lobar degeneration and associated imaging diagnostic errors. , 2011, Archives of neurology.

[44]  M. James,et al.  [11C]-DPA-713 and [18F]-DPA-714 as New PET Tracers for TSPO: A Comparison with [11C]-(R)-PK11195 in a Rat Model of Herpes Encephalitis , 2009, Molecular Imaging and Biology.

[45]  C. Wiley,et al.  Imaging Microglial Activation During Neuroinflammation and Alzheimer’s Disease , 2009, Journal of Neuroimmune Pharmacology.

[46]  Elizabeth L Sampson,et al.  In vivo detection of microglial activation in frontotemporal dementia , 2004, Annals of neurology.

[47]  Julie Price,et al.  Carbon 11-labeled Pittsburgh Compound B and carbon 11-labeled (R)-PK11195 positron emission tomographic imaging in Alzheimer disease. , 2009, Archives of neurology.

[48]  Alan A. Wilson,et al.  Positron-emission tomography imaging of the TSPO with [(18)F]FEPPA in a preclinical breast cancer model. , 2013, Cancer biotherapy & radiopharmaceuticals.

[49]  Y. Huang,et al.  Peripheral lipopolysaccharide (LPS) challenge promotes microglial hyperactivity in aged mice that is associated with exaggerated induction of both pro-inflammatory IL-1β and anti-inflammatory IL-10 cytokines , 2009, Brain, Behavior, and Immunity.

[50]  Shane M. Wilkinson,et al.  [18F]DPA-714: Direct Comparison with [11C]PK11195 in a Model of Cerebral Ischemia in Rats , 2013, PloS one.

[51]  David Mann,et al.  Frontotemporal lobar degeneration: clinical and pathological relationships , 2007, Acta Neuropathologica.

[52]  William B Goggins,et al.  Effects of 17-allylamino-17-demethoxygeldanamycin (17-AAG) in transgenic mouse models of frontotemporal lobar degeneration and Alzheimer’s disease , 2013, Translational Neurodegeneration.

[53]  Xiaoyuan Chen,et al.  Longitudinal PET Imaging of Muscular Inflammation Using 18F-DPA-714 and 18F-Alfatide II and Differentiation with Tumors , 2014, Theranostics.

[54]  K. Blennow,et al.  Increased intrathecal inflammatory activity in frontotemporal dementia: pathophysiological implications , 2004, Journal of Neurology, Neurosurgery & Psychiatry.

[55]  V. Ikonomidou,et al.  Translocator Protein PET Imaging for Glial Activation in Multiple Sclerosis , 2011, Journal of Neuroimmune Pharmacology.

[56]  Denis Guilloteau,et al.  DPA-714, a New Translocator Protein–Specific Ligand: Synthesis, Radiofluorination, and Pharmacologic Characterization , 2008, Journal of Nuclear Medicine.

[57]  T. Patterson,et al.  Assessment of Potential Neuronal Toxicity of Inhaled Anesthetics in the Developing Nonhuman Primate , 2012 .

[58]  Alan A. Wilson,et al.  Translocator Protein (18 kDa) Polymorphism (rs6971) Explains in-vivo Brain Binding Affinity of the PET Radioligand [18F]-FEPPA , 2012, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[59]  R. Ransohoff,et al.  Regulation of Tau Pathology by the Microglial Fractalkine Receptor , 2010, Neuron.

[60]  Alan A. Wilson,et al.  Comparison of [11C]PBR28 and [18F]FEPPA as CNS peripheral benzodiazepine receptor PET ligands in the pig , 2008 .

[61]  Bertrand Tavitian,et al.  Noninvasive molecular imaging of neuroinflammation , 2012, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[62]  C. Wiley,et al.  The Positron Emission Tomography Ligand DAA1106 Binds With High Affinity to Activated Microglia in Human Neurological Disorders , 2008, Journal of neuropathology and experimental neurology.

[63]  Roger N Gunn,et al.  An 18-kDa Translocator Protein (TSPO) polymorphism explains differences in binding affinity of the PET radioligand PBR28 , 2011, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[64]  B. Gulyás,et al.  In vivo TSPO imaging in patients with multiple sclerosis: a brain PET study with [18F]FEDAA1106 , 2013, EJNMMI Research.

[65]  M. Grégoire,et al.  In vivo imaging of neuroinflammation: a comparative study between [18F]PBR111, [11C]CLINME and [11C]PK11195 in an acute rodent model , 2010, European Journal of Nuclear Medicine and Molecular Imaging.

[66]  R. Boisgard,et al.  In vivo Evaluation of Inflammatory Bowel Disease with the Aid of μPET and the Translocator Protein 18 kDa Radioligand [18F]DPA-714 , 2014, Molecular Imaging and Biology.

[67]  Michael T. Heneka,et al.  Innate immune activation in neurodegenerative disease , 2014, Nature Reviews Immunology.

[68]  P. Mcgeer,et al.  Inflammation and the Degenerative Diseases of Aging , 2004, Annals of the New York Academy of Sciences.

[69]  Alan A. Wilson,et al.  Quantitative imaging of neuroinflammation in human white matter: A positron emission tomography study with translocator protein 18 kDa radioligand, [18F]‐FEPPA , 2014, Synapse.

[70]  Alan A. Wilson,et al.  Whole Body Biodistribution and Radiation Dosimetry in Humans of a New PET Ligand, [18F]-FEPPA, to Image Translocator Protein (18 kDa) , 2013, Molecular Imaging and Biology.

[71]  Caroline Prunier,et al.  Molecular Imaging of Microglial Activation in Amyotrophic Lateral Sclerosis , 2012, PloS one.

[72]  B. Gulyás,et al.  In vivo imaging of the 18-kDa translocator protein (TSPO) with [18F]FEDAA1106 and PET does not show increased binding in Alzheimer’s disease patients , 2013, European Journal of Nuclear Medicine and Molecular Imaging.

[73]  Ted M. Dawson,et al.  Inducible nitric oxide synthase stimulates dopaminergic neurodegeneration in the MPTP model of Parkinson disease , 1999, Nature Medicine.

[74]  Francis J McMahon,et al.  In vivo radioligand binding to translocator protein correlates with severity of Alzheimer's disease. , 2013, Brain : a journal of neurology.

[75]  S. Meikle,et al.  In vivo evidence for microglial activation in neurodegenerative dementia , 2006, Acta neurologica Scandinavica. Supplementum.

[76]  Roger N Gunn,et al.  Two Binding Sites for [3H]PBR28 in Human Brain: Implications for TSPO PET Imaging of Neuroinflammation , 2010, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[77]  A. Lammertsma,et al.  Promising potential of new generation translocator protein tracers providing enhanced contrast of arthritis imaging by positron emission tomography in a rat model of arthritis , 2014, Arthritis Research & Therapy.

[78]  Alan A. Wilson,et al.  Neuroinflammation in healthy aging: A PET study using a novel Translocator Protein 18kDa (TSPO) radioligand, [18F]-FEPPA , 2014, NeuroImage.

[79]  C. Hommet,et al.  Neuroinflammation and β Amyloid Deposition in Alzheimer's Disease: In vivo Quantification with Molecular Imaging , 2013, Dementia and Geriatric Cognitive Disorders.

[80]  S. Rollinson,et al.  Patterns of microglial cell activation in frontotemporal lobar degeneration , 2014, Neuropathology and applied neurobiology.

[81]  Sylvain Houle,et al.  Radiosynthesis and initial evaluation of [18F]-FEPPA for PET imaging of peripheral benzodiazepine receptors. , 2008, Nuclear medicine and biology.

[82]  Bin Zhang,et al.  Synapse Loss and Microglial Activation Precede Tangles in a P301S Tauopathy Mouse Model , 2007, Neuron.

[83]  L. Borza.  A review on the cause-effect relationship between oxidative stress and toxic proteins in the pathogenesis of neurodegenerative diseases. , 2014, Revista medico-chirurgicala a Societatii de Medici si Naturalisti din Iasi.

[84]  D J Brooks,et al.  Comparison of Methods for Analysis of Clinical [11C]Raclopride Studies , 1996, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.