Sifting through the surfeit of neuroinflammation tracers

The first phase of molecular brain imaging of microglial activation in neuroinflammatory conditions began some 20 years ago with the introduction of [11C]-(R)-PK11195, the prototype isoquinoline ligand for translocator protein (18 kDa) (TSPO). Investigations by positron emission tomography (PET) revealed microgliosis in numerous brain diseases, despite the rather low specific binding signal imparted by [11C]-(R)-PK11195. There has since been enormous expansion of the repertoire of TSPO tracers, many with higher specific binding, albeit complicated by allelic dependence of the affinity. However, the specificity of TSPO PET for revealing microglial activation not been fully established, and it has been difficult to judge the relative merits of the competing tracers and analysis methods with respect to their sensitivity for detecting microglial activation. We therefore present a systematic comparison of 13 TSPO PET and single photon computed tomography (SPECT) tracers belonging to five structural classes, each of which has been investigated by compartmental analysis in healthy human brain relative to a metabolite-corrected arterial input. We emphasize the need to establish the non-displaceable binding component for each ligand and conclude with five recommendations for a standard approach to define the cellular distribution of TSPO signals, and to characterize the properties of candidate TSPO tracers.

[1]  Jennifer M. Coughlin,et al.  Translational evaluation of translocator protein as a marker of neuroinflammation in schizophrenia , 2018, Molecular Psychiatry.

[2]  Roger N Gunn,et al.  11C-DPA-713 has much greater specific binding to translocator protein 18 kDa (TSPO) in human brain than 11C-(R)-PK11195 , 2017, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[3]  N. Albert,et al.  TSPO PET for glioma imaging using the novel ligand 18F-GE-180: first results in patients with glioblastoma , 2017, European Journal of Nuclear Medicine and Molecular Imaging.

[4]  Pontus Plavén-Sigray,et al.  Assessment of simplified ratio-based approaches for quantification of PET [11C]PBR28 data , 2017, EJNMMI Research.

[5]  C. Svarer,et al.  The Variability of Translocator Protein Signal in Brain and Blood of Genotyped Healthy Humans Using In Vivo 123I-CLINDE SPECT Imaging: A Test–Retest Study , 2017, The Journal of Nuclear Medicine.

[6]  P. Matthews,et al.  Pro-inflammatory activation of primary microglia and macrophages increases 18 kDa translocator protein expression in rodents but not humans , 2017, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[7]  N. Mori,et al.  Depiction of microglial activation in aging and dementia: Positron emission tomography with [11C]DPA713 versus [11C](R)PK11195 , 2017, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[8]  H. Ohba,et al.  Quantification of ONO-2952 Occupancy of 18-kDaTranslocator Protein in Conscious Monkey Brains using Positron Emission Tomography , 2017, The Journal of Pharmacology and Experimental Therapeutics.

[9]  R. Narendran,et al.  Brain translocator protein occupancy by ONO‐2952 in healthy adults: A Phase 1 PET study using [11C]PBR28 , 2017, Synapse.

[10]  Talakad G. Lohith,et al.  11C-ER176, a Radioligand for 18-kDa Translocator Protein, Has Adequate Sensitivity to Robustly Image All Three Affinity Genotypes in Human Brain , 2017, The Journal of Nuclear Medicine.

[11]  R. Banati,et al.  Epigenetic Silencing of the Human 18 kDa Translocator Protein in a T Cell Leukemia Cell Line. , 2017, DNA and cell biology.

[12]  M. Ewers,et al.  Increase of TREM2 during Aging of an Alzheimer’s Disease Mouse Model Is Paralleled by Microglial Activation and Amyloidosis , 2017, Front. Aging Neurosci..

[13]  R. Banati,et al.  Functional gains in energy and cell metabolism after TSPO gene insertion , 2017, Cell cycle.

[14]  I. Buvat,et al.  Acute Morphine Exposure Increases the Brain Distribution of [18F]DPA-714, a PET Biomarker of Glial Activation in Nonhuman Primates , 2016, The international journal of neuropsychopharmacology.

[15]  A. Meyer-Lindenberg,et al.  Microglia Activation and Schizophrenia: Lessons From the Effects of Minocycline on Postnatal Neurogenesis, Neuronal Survival and Synaptic Pruning. , 2016, Schizophrenia bulletin.

[16]  I. Buvat,et al.  Impact of endothelial TSPO on the quantification of 18 F-DPA-714 , 2017 .

[17]  Jennifer M. Coughlin,et al.  Imaging of Glial Cell Activation and White Matter Integrity in Brains of Active and Recently Retired National Football League Players , 2017, JAMA neurology.

[18]  F. Turkheimer,et al.  Pseudo-reference regions for glial imaging with 11 C-PBR28: investigation in two clinical cohorts , 2017 .

[19]  M. Fulham,et al.  Preclinical in vivo and in vitro comparison of the translocator protein PET ligands [18F]PBR102 and [18F]PBR111 , 2017, European Journal of Nuclear Medicine and Molecular Imaging.

[20]  Wei He,et al.  Global Deletion of TSPO Does Not Affect the Viability and Gene Expression Profile , 2016, PloS one.

[21]  R. Hinz,et al.  In vivo imaging of brain microglial activity in antipsychotic-free and medicated schizophrenia: a [11C](R)-PK11195 positron emission tomography study , 2016, Molecular Psychiatry.

[22]  R. Banati,et al.  The impact of high and low dose ionising radiation on the central nervous system , 2016, Redox biology.

[23]  D. Sharp,et al.  Kinetic analysis of the translocator protein positron emission tomography ligand [18F]GE-180 in the human brain , 2016, European Journal of Nuclear Medicine and Molecular Imaging.

[24]  A. Waldman,et al.  Flutriciclamide (18F-GE180) PET: First-in-Human PET Study of Novel Third-Generation In Vivo Marker of Human Translocator Protein , 2016, The Journal of Nuclear Medicine.

[25]  Response to Narendran and Frankle: The Interpretation of PET Microglial Imaging in Schizophrenia. , 2016, The American journal of psychiatry.

[26]  R. Narendran,et al.  Comment on Analyses and Conclusions of "Microglial Activity in People at Ultra High Risk of Psychosis and in Schizophrenia: An [(11)C]PBR28 PET Brain Imaging Study". , 2016, The American journal of psychiatry.

[27]  Simon Cervenka,et al.  In vivo evidence of a functional association between immune cells in blood and brain in healthy human subjects , 2016, Brain, Behavior, and Immunity.

[28]  Jennifer M. Coughlin,et al.  In vivo markers of inflammatory response in recent-onset schizophrenia: a combined study using [11C]DPA-713 PET and analysis of CSF and plasma , 2016, Translational Psychiatry.

[29]  Adriaan A Lammertsma,et al.  Imaging of neuroinflammation in Alzheimer's disease, multiple sclerosis and stroke: Recent developments in positron emission tomography. , 2016, Biochimica et biophysica acta.

[30]  D. Stocco,et al.  Translocator Protein (TSPO) Affects Mitochondrial Fatty Acid Oxidation in Steroidogenic Cells. , 2016, Endocrinology.

[31]  Kanako Morohaku,et al.  Mitochondrial Translocator Protein (TSPO) Function Is Not Essential for Heme Biosynthesis* , 2015, The Journal of Biological Chemistry.

[32]  P. Cumming,et al.  Specific binding of [18F]fluoroethyl‐harmol to monoamine oxidase A in rat brain cryostat sections, and compartmental analysis of binding in living brain , 2015, Journal of neurochemistry.

[33]  Yiyun Huang,et al.  Imaging robust microglial activation after lipopolysaccharide administration in humans with PET , 2015, Proceedings of the National Academy of Sciences.

[34]  R. Boisgard,et al.  Novel Pyrazolo[1,5-a]pyrimidines as Translocator Protein 18 kDa (TSPO) Ligands: Synthesis, in Vitro Biological Evaluation, [(18)F]-Labeling, and in Vivo Neuroinflammation PET Images. , 2015, Journal of medicinal chemistry.

[35]  Kimberly J. Jenko,et al.  Neuroinflammation in Temporal Lobe Epilepsy Measured Using Positron Emission Tomographic Imaging of Translocator Protein. , 2015, JAMA neurology.

[36]  Y. Fontyn,et al.  Differential influence of propofol and isoflurane anesthesia in a non‐human primate on the brain kinetics and binding of [18F]DPA‐714, a positron emission tomography imaging marker of glial activation , 2015, European Journal of Neuroscience.

[37]  P. Remy,et al.  Optimized Quantification of Translocator Protein Radioligand 18F-DPA-714 Uptake in the Brain of Genotyped Healthy Volunteers , 2015, The Journal of Nuclear Medicine.

[38]  D. Brooks,et al.  Can Studies of Neuroinflammation in a TSPO Genetic Subgroup (HAB or MAB) Be Applied to the Entire AD Cohort? , 2015, The Journal of Nuclear Medicine.

[39]  O. Garaschuk,et al.  Neuroinflammation in Alzheimer's disease , 2015, The Lancet Neurology.

[40]  Jean-Dominique Gallezot,et al.  Comparison of standardized uptake values with volume of distribution for quantitation of [(11)C]PBR28 brain uptake. , 2015, Nuclear medicine and biology.

[41]  Alan A. Wilson,et al.  Role of translocator protein density, a marker of neuroinflammation, in the brain during major depressive episodes. , 2015, JAMA psychiatry.

[42]  R. Boellaard,et al.  Quantification of [18F]DPA-714 binding in the human brain: initial studies in healthy controls and Alzheimer's disease patients , 2015, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[43]  G. Searle,et al.  The Simplified Reference Tissue Model: Model Assumption Violations and Their Impact on Binding Potential , 2015, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[44]  R. Garavito,et al.  Crystal structures of translocator protein (TSPO) and mutant mimic of a human polymorphism , 2015, Science.

[45]  Wayne A Hendrickson,et al.  Structure and activity of tryptophan-rich TSPO proteins , 2015, Science.

[46]  C. Halldin,et al.  Test–retest reproducibility of [11C]PBR28 binding to TSPO in healthy control subjects , 2015, European Journal of Nuclear Medicine and Molecular Imaging.

[47]  E. Rabiner,et al.  Positron emission tomography imaging of the 18-kDa translocator protein (TSPO) with [18F]FEMPA in Alzheimer’s disease patients and control subjects , 2015, European Journal of Nuclear Medicine and Molecular Imaging.

[48]  C. Svarer,et al.  In Vivo Quantification of Cerebral Translocator Protein Binding in Humans Using 6-Chloro-2-(4′-123I-Iodophenyl)-3-(N,N-Diethyl)-Imidazo[1,2-a]Pyridine-3-Acetamide SPECT , 2014, The Journal of Nuclear Medicine.

[49]  David Zahra,et al.  Positron emission tomography and functional characterization of a complete PBR/TSPO knockout , 2014, Nature Communications.

[50]  A. McAllister,et al.  Alterations in Immune Cells and Mediators in the Brain: It's Not Always Neuroinflammation! , 2014, Brain pathology.

[51]  Adam J. Svahn,et al.  Emergent Properties of Microglia , 2014, Brain pathology.

[52]  M. Graeber Neuroinflammation: No Rose by Any Other Name , 2014, Brain pathology.

[53]  Richard B. Banati,et al.  The 18 kDa Translocator Protein, Microglia and Neuroinflammation , 2014, Brain pathology.

[54]  Kimberly J. Jenko,et al.  Synthesis and Evaluation of Translocator 18 kDa Protein (TSPO) Positron Emission Tomography (PET) Radioligands with Low Binding Sensitivity to Human Single Nucleotide Polymorphism rs6971 , 2014, ACS chemical neuroscience.

[55]  D. Stocco,et al.  Peripheral Benzodiazepine Receptor/Translocator Protein Global Knock-out Mice Are Viable with No Effects on Steroid Hormone Biosynthesis*♦ , 2014, The Journal of Biological Chemistry.

[56]  A. Arefin,et al.  ‘Neuroinflammation’ differs categorically from inflammation: transcriptomes of Alzheimer's disease, Parkinson's disease, schizophrenia and inflammatory diseases compared , 2014, neurogenetics.

[57]  P. Cumming,et al.  Radiosynthesis and Validation of 18F-FP-CMT, a Phenyltropane with Superior Properties for Imaging the Dopamine Transporter in Living Brain , 2014, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[58]  F. Ricchelli,et al.  Regulation of the Mitochondrial Permeability Transition Pore by the Outer Membrane Does Not Involve the Peripheral Benzodiazepine Receptor (Translocator Protein of 18 kDa (TSPO))* , 2014, The Journal of Biological Chemistry.

[59]  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.

[60]  S. Becker,et al.  Structure of the Mitochondrial Translocator Protein in Complex with a Diagnostic Ligand , 2014, Science.

[61]  Paul M. Matthews,et al.  Eratum: Determination of [ 11 C]PBR28 binding potential in vivo: A first human TSPO blocking study (Journal of Cerebral Blood Flow and Metabolism (2014) 34 (1256)) , 2014 .

[62]  W. R. Butler,et al.  Translocator protein/peripheral benzodiazepine receptor is not required for steroid hormone biosynthesis. , 2014, Endocrinology.

[63]  Roger N Gunn,et al.  Quantification of the Specific Translocator Protein Signal of 18F-PBR111 in Healthy Humans: A Genetic Polymorphism Effect on In Vivo Binding , 2013, The Journal of Nuclear Medicine.

[64]  R. Carson,et al.  The neuroinflammation marker translocator protein is not elevated in individuals with mild-to-moderate depression: A [11C]PBR28 PET study , 2013, Brain, Behavior, and Immunity.

[65]  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.

[66]  Kimberly J. Jenko,et al.  A Genetic Polymorphism for Translocator Protein 18 Kda Affects both in Vitro and in Vivo Radioligand Binding in Human Brain to this Putative Biomarker of Neuroinflammation , 2013, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[67]  Annelaure Damont,et al.  Metabolism and Quantification of [18F]DPA-714, a New TSPO Positron Emission Tomography Radioligand , 2013, Drug Metabolism and Disposition.

[68]  Philippe Hantraye,et al.  Reactive Astrocytes Overexpress TSPO and Are Detected by TSPO Positron Emission Tomography Imaging , 2012, The Journal of Neuroscience.

[69]  G. Bormans,et al.  Preclinical evaluation and quantification of [18F]MK-9470 as a radioligand for PET imaging of the type 1 cannabinoid receptor in rat brain , 2012, European Journal of Nuclear Medicine and Molecular Imaging.

[70]  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.

[71]  Ronald Boellaard,et al.  Optimization of supervised cluster analysis for extracting reference tissue input curves in (R)-[11C]PK11195 brain PET studies , 2012, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[72]  V. Papadopoulos,et al.  Structural and functional evolution of the translocator protein (18 kDa). , 2012, Current molecular medicine.

[73]  M. Gavish,et al.  The 18 kDa mitochondrial translocator protein (TSPO) prevents accumulation of protoporphyrin IX. Involvement of reactive oxygen species (ROS). , 2012, Current molecular medicine.

[74]  M. Gavish,et al.  The role of 18 kDa mitochondrial translocator protein (TSPO) in programmed cell death, and effects of steroids on TSPO expression. , 2012, Current molecular medicine.

[75]  Christer Halldin,et al.  Kinetic analysis and test-retest variability of the radioligand [11C](R)-PK11195 binding to TSPO in the human brain - a PET study in control subjects , 2012, EJNMMI Research.

[76]  M. Thaning,et al.  [¹⁸F]GE-180: a novel fluorine-18 labelled PET tracer for imaging Translocator protein 18 kDa (TSPO). , 2012, Bioorganic & medicinal chemistry letters.

[77]  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.

[78]  D. Flockerzi,et al.  Modeling the light- and redox-dependent interaction of PpsR/AppA in Rhodobacter sphaeroides. , 2011, Biophysical journal.

[79]  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.

[80]  M. Grégoire,et al.  Evaluation of [123I]-CLINDE as a potent SPECT radiotracer to assess the degree of astroglia activation in cuprizone-induced neuroinflammation , 2011, European Journal of Nuclear Medicine and Molecular Imaging.

[81]  M. Berk,et al.  eview athways underlying neuroprogression in bipolar disorder : Focus on nflammation , oxidative stress and neurotrophic factors , 2010 .

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

[83]  T. Guilarte,et al.  Imaging glial cell activation with [11C]-R-PK11195 in patients with AIDS , 2005, Journal of NeuroVirology.

[84]  M. Fulham,et al.  A rapid solid-phase extraction method for measurement of non-metabolised peripheral benzodiazepine receptor ligands, [(18)F]PBR102 and [(18)F]PBR111, in rat and primate plasma. , 2011, Nuclear medicine and biology.

[85]  Koen Van Laere,et al.  Preclinical Evaluation of 18F-JNJ41510417 as a Radioligand for PET Imaging of Phosphodiesterase-10A in the Brain , 2010, The Journal of Nuclear Medicine.

[86]  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.

[87]  A. Reynolds,et al.  The development of PET radioligands for imaging the translocator protein (18 kDa): What have we learned? , 2010 .

[88]  Masahiro Fujita,et al.  Comparison of [11C]-(R)-PK 11195 and [11C]PBR28, two radioligands for translocator protein (18 kDa) in human and monkey: Implications for positron emission tomographic imaging of this inflammation biomarker , 2010, NeuroImage.

[89]  M. Gavish,et al.  Potential involvement of F0F1-ATP(synth)ase and reactive oxygen species in apoptosis induction by the antineoplastic agent erucylphosphohomocholine in glioblastoma cell lines , 2010, Apoptosis.

[90]  M. Pomper,et al.  Initial Evaluation of 11C-DPA-713, a Novel TSPO PET Ligand, in Humans , 2009, Journal of Nuclear Medicine.

[91]  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.

[92]  J. Goverman Autoimmune T cell responses in the central nervous system , 2009, Nature Reviews Immunology.

[93]  I. Hickie,et al.  Therapeutic signposts: using biomarkers to guide better treatment of schizophrenia and other psychotic disorders , 2009, The Medical journal of Australia.

[94]  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.

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

[96]  Ming-Kai Chen,et al.  Translocator protein 18 kDa (TSPO): molecular sensor of brain injury and repair. , 2008, Pharmacology & therapeutics.

[97]  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.

[98]  K. Mardon,et al.  Pharmacological evaluation of [123I]-CLINDE: a radioiodinated imidazopyridine-3-acetamide for the study of peripheral benzodiazepine binding sites (PBBS) , 2008, European Journal of Nuclear Medicine and Molecular Imaging.

[99]  Jeih-San Liow,et al.  Radiation Dosimetry and Biodistribution in Monkey and Man of 11C-PBR28: A PET Radioligand to Image Inflammation , 2007, Journal of Nuclear Medicine.

[100]  Tetsuya Suhara,et al.  A comparison of the high‐affinity peripheral benzodiazepine receptor ligands DAA1106 and (R)‐PK11195 in rat models of neuroinflammation: implications for PET imaging of microglial activation , 2007, Journal of neurochemistry.

[101]  Masahiro Fujita,et al.  Kinetic evaluation in nonhuman primates of two new PET ligands for peripheral benzodiazepine receptors in brain , 2007, Synapse.

[102]  Lars H. Pinborg,et al.  [123I]Epidepride binding to cerebellar dopamine D2/D3 receptors is displaceable: Implications for the use of cerebellum as a reference region , 2007, NeuroImage.

[103]  Marie-Claude Asselin,et al.  Quantification of PET Studies with the Very High-Affinity Dopamine D2/D3 Receptor Ligand [11C]FLB 457: Re-Evaluation of the Validity of using a Cerebellar Reference Region , 2007, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[104]  Ryuji Nakao,et al.  Quantitative Analysis for Estimating Binding Potential of the Peripheral Benzodiazepine Receptor with [11C]DAA1106 , 2007, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[105]  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.

[106]  D. Nutt,et al.  Translocator protein (18kDa): new nomenclature for the peripheral-type benzodiazepine receptor based on its structure and molecular function. , 2006, Trends in pharmacological sciences.

[107]  Paul Cumming,et al.  Up‐regulation of PK11195 binding in areas of axonal degeneration coincides with early microglial activation in mouse brain , 2006, The European journal of neuroscience.

[108]  Paul Cumming,et al.  Distribution of PK11195 binding sites in porcine brain studied by autoradiography in vitro and by positron emission tomography , 2006, Synapse.

[109]  Paul Cumming,et al.  Peripheral benzodiazepine receptors in the brain of cirrhosis patients with manifest hepatic encephalopathy , 2006, European Journal of Nuclear Medicine and Molecular Imaging.

[110]  Ronald Boellaard,et al.  Development of a Tracer Kinetic Plasma Input Model for (R)-[11C]PK11195 Brain Studies , 2005, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[111]  Alexander Gerhard,et al.  Evolution of microglial activation in patients after ischemic stroke: a [11C](R)-PK11195 PET study , 2005, NeuroImage.

[112]  Yuji Nagai,et al.  Novel peripheral benzodiazepine receptor ligand [11C]DAA1106 for PET: An imaging tool for glial cells in the brain , 2004, Synapse.

[113]  V. Papadopoulos,et al.  A novel Arabidopsis thaliana protein is a functional peripheral-type benzodiazepine receptor. , 2004, Plant & cell physiology.

[114]  E. Hamel,et al.  Assessment of the peripheral benzodiazepine receptors in human gliomas by two methods , 1998, Journal of Neuro-Oncology.

[115]  R B Banati,et al.  [11C](R)-PK11195 PET imaging of microglial activation in multiple system atrophy , 2003, Neurology.

[116]  A. Gee,et al.  The peripheral benzodiazepine receptor ligand PK11195 binds with high affinity to the acute phase reactant alpha1-acid glycoprotein: implications for the use of the ligand as a CNS inflammatory marker. , 2003, Nuclear medicine and biology.

[117]  T. Suhara,et al.  [18F]FMDAA1106 and [18F]FEDAA1106: two positron-emitter labeled ligands for peripheral benzodiazepine receptor (PBR). , 2003, Bioorganic & medicinal chemistry letters.

[118]  R. Banati Brain plasticity and microglia: is transsynaptic glial activation in the thalamus after limb denervation linked to cortical plasticity and central sensitisation? , 2002, Journal of Physiology-Paris.

[119]  R. Myers,et al.  Long-term trans-synaptic glial responses in the human thalamus after peripheral nerve injury , 2001, Neuroreport.

[120]  R B Banati,et al.  In vivo visualization of activated glia by [11C] (R)-PK11195-PET following herpes encephalitis reveals projected neuronal damage beyond the primary focal lesion. , 2001, Brain : a journal of neurology.

[121]  Roger N Gunn,et al.  In-vivo measurement of activated microglia in dementia , 2001, The Lancet.

[122]  A. Gjedde,et al.  Normalization of markers for dopamine innervation in striatum of MPTP‐lesioned miniature pigs with intrastriatal grafts , 2001, Acta neurologica Scandinavica.

[123]  R B Banati,et al.  The peripheral benzodiazepine binding site in the brain in multiple sclerosis: quantitative in vivo imaging of microglia as a measure of disease activity. , 2000, Brain : a journal of neurology.

[124]  R B Banati,et al.  Thalamic microglial activation in ischemic stroke detected in vivo by PET and [11C]PK11195 , 2000, Neurology.

[125]  R. Brown,et al.  Location-dependent role of the human glioma cell peripheral-type benzodiazepine receptor in proliferation and steroid biosynthesis. , 2000, Cancer letters.

[126]  T. Guilarte,et al.  Cellular and Subcellular Localization of Peripheral Benzodiazepine Receptors After Trimethyltin Neurotoxicity , 2000, Journal of neurochemistry.

[127]  G. Slegers,et al.  High-performance liquid chromatographic determination of [11C]1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline carboxamide in mouse plasma and tissue and in human plasma. , 1999, Journal of chromatography. B, Biomedical sciences and applications.

[128]  F E Turkheimer,et al.  [11C](R)-PK11195 positron emission tomography imaging of activated microglia in vivo in Rasmussen’s encephalitis , 1999, Neurology.

[129]  Abraham Weizman,et al.  Enigma of the peripheral benzodiazepine receptor. , 1999, Pharmacological reviews.

[130]  S. Chaki,et al.  Binding characteristics of [3H]DAA1106, a novel and selective ligand for peripheral benzodiazepine receptors. , 1999, European journal of pharmacology.

[131]  V. Papadopoulos,et al.  Peripheral-type benzodiazepine receptor (PBR) in human breast cancer: correlation of breast cancer cell aggressive phenotype with PBR expression, nuclear localization, and PBR-mediated cell proliferation and nuclear transport of cholesterol. , 1999, Cancer research.

[132]  V. Papadopoulos,et al.  Printed in U.S.A. Copyright © 1998 by The Endocrine Society Peripheral-Type Benzodiazepine Receptor Function in Cholesterol Transport. Identification of a Putative Cholesterol Recognition/Interaction Amino Acid Sequence and Consensus Pattern* , 2022 .

[133]  M. Snyder,et al.  Evidence for a diazepam-binding inhibitor (DBI) benzodiazepine receptor-like mechanism in ecdysteroidogenesis by the insect prothoracic gland , 1998, Cell and Tissue Research.

[134]  G. Kroemer,et al.  PK11195, a ligand of the mitochondrial benzodiazepine receptor, facilitates the induction of apoptosis and reverses Bcl-2-mediated cytoprotection. , 1998, Experimental cell research.

[135]  A. A. Yeliseev,et al.  A mammalian mitochondrial drug receptor functions as a bacterial "oxygen" sensor. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[136]  R B Banati,et al.  PK (‘peripheral benzodiazepine’) – binding sites in the CNS indicate early and discrete brain lesions: microautoradiographic detection of [3H]PK 11195 binding to activated microglia , 1997, Journal of neurocytology.

[137]  V. Papadopoulos,et al.  Peripheral benzodiazepine receptor in cholesterol transport and steroidogenesis , 1997, Steroids.

[138]  D. Williams,et al.  Two cellular and subcellular locations for the peripheral-type benzodiazepine receptor in rat liver. , 1996, Biochemical pharmacology.

[139]  H. Alho,et al.  Expression of mitochondrial benzodiazepine receptor and its putative endogenous ligand diazepam binding inhibitor in cultured primary astrocytes and C-6 cells: relation to cell growth. , 1994, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

[140]  Peter Herscovitch,et al.  Comparison of Bolus and Infusion Methods for Receptor Quantitation: Application to [18F]Cyclofoxy and Positron Emission Tomography , 1993, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[141]  P. Casellas,et al.  Distribution profile and properties of peripheral-type benzodiazepine receptors on human hemopoietic cells. , 1993, Life sciences.

[142]  J. Regan,et al.  Cloning and expression of a pharmacologically unique bovine peripheral-type benzodiazepine receptor isoquinoline binding protein. , 1991, The Journal of biological chemistry.

[143]  V. Papadopoulos,et al.  Peripheral-type benzodiazepine receptors mediate translocation of cholesterol from outer to inner mitochondrial membranes in adrenocortical cells. , 1990, The Journal of biological chemistry.

[144]  H. Vinters,et al.  Specific high‐affinity binding of peripheral benzodiazepine receptor ligands to brain tumors in rat and man , 1990, Cancer.

[145]  M. Santi,et al.  Molecular cloning and expression of cDNA encoding a peripheral-type benzodiazepine receptor. , 1989, The Journal of biological chemistry.

[146]  E. Costa,et al.  Mitochondrial benzodiazepine receptors regulate steroid biosynthesis. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[147]  G. L. Watkins,et al.  PET Imaging of human gliomas with ligands for the peripheral benzodiazepine binding site , 1989, Annals of neurology.

[148]  T. F. Murray,et al.  Differential Binding Properties of the Peripheral‐Type Benzodiazepine Ligands [3H]PK 11195 and [3H]Ro 5‐4864 in Trout and Mouse Brain Membranes , 1989, Journal of neurochemistry.

[149]  T D Lee,et al.  Identification of des-(Gly-Ile)-endozepine as an effector of corticotropin-dependent adrenal steroidogenesis: stimulation of cholesterol delivery is mediated by the peripheral benzodiazepine receptor. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[150]  J. Hirsch,et al.  Mitochondrial benzodiazepine receptors mediate inhibition of mitochondrial respiratory control. , 1989, Molecular pharmacology.

[151]  A. Guidotti,et al.  Molecular characterization and mitochondrial density of a recognition site for peripheral-type benzodiazepine ligands. , 1988, Molecular pharmacology.

[152]  P. Skolnick,et al.  Maximal electroshock increases the density of [3H]Ro 5-4864 binding to mouse cerebral cortex , 1987, Brain Research Bulletin.

[153]  J. Morgan,et al.  Benzodiazepines that bind at peripheral sites inhibit cell proliferation. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[154]  G. Le Fur,et al.  Peripheral benzodiazepine binding sites: effect of PK 11195, 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide. I. In vitro studies. , 1983, Life sciences.

[155]  H. Schoemaker,et al.  Specific high-affinity saturable binding of [3H] R05-4864 to benzodiazepine binding sites in the rat cerebral cortex. , 1981, European journal of pharmacology.

[156]  C. Braestrup,et al.  Specific benzodiazepine receptors in rat brain characterized by high-affinity (3H)diazepam binding. , 1977, Proceedings of the National Academy of Sciences of the United States of America.