PET radioligands for in vivo visualization of neuroinflammation

Current Pharmaceutical Design

Volumn 20, Issue 37, 2014, Pages 5897-5913

  Ory, Dieter ^a   Celen, Sofie ^a   Verbruggen, Alfons ^a   Bormans, Guy ^a  

^a UNIVERSITY OF LEUVEN   (Belgium)

Author keywords

Neuroinflammation; Positron emission tomography

Indexed keywords

1 (2,3 DICHLOROBENZOYL) 5 METHOXY 2 METHYL 3 (2 MORPHOLINOETHYL)INDOLE; CANNABINOID; CANNABINOID 2 RECEPTOR; CARBON 11; CELECOXIB; CLINME C11; COPPER 64; CYCLOOXYGENASE 2 INHIBITOR; DAA 1106 C 11; DPA 713 C 11; DPA 714 F 18; FEPPA I 18; FLUORINE 18; FMDAA1106 F 18; GALLIUM 68; GE 180 F 18; IODINE 124; N SEC BUTYL 1 (2 CHLOROPHENYL) N METHYL 3 ISOQUINOLINECARBOXAMIDE C 11; NITROGEN 13; NONSTEROID ANTIINFLAMMATORY AGENT; OXOQUINOLINE F 18; OXYGEN 15; PBR 01 C 11; PBR 06 C 11; PBR 111 F 18; PBR 28 C 11; RADIOPHARMACEUTICAL AGENT; SSR 180575 C 11; UNCLASSIFIED DRUG; UNINDEXED DRUG; ZIRCONIUM; LIGAND; TRACER;

ARTICLE; BINDING AFFINITY; DISEASE COURSE; HUMAN; IN VIVO STUDY; INNATE IMMUNITY; NERVOUS SYSTEM INFLAMMATION; NONHUMAN; POSITRON EMISSION TOMOGRAPHY; PROTEIN EXPRESSION; ANIMAL; DEGENERATIVE DISEASE; METABOLISM; PATHOLOGY; RADIOASSAY;

ANIMALS; HUMANS; LIGANDS; NEURODEGENERATIVE DISEASES; POSITRON-EMISSION TOMOGRAPHY; RADIOACTIVE TRACERS; RADIOLIGAND ASSAY;

EID: 84911485957     PISSN: 13816128     EISSN: 18734286     Source Type: Journal    
DOI: 10.2174/1381612820666140613120212     Document Type: Article

References (231)

1. Graeber MB, Li W, Rodriguez ML. Role of microglia in CNS inflammation. FEBS Lett 2011; 585: 3798-805.
2. Jacobs AH, Tavitian B. Noninvasive molecular imaging of neuroinflammation. J Cereb Blood Flow Metab 2012; 32: 1393-415.
3. Chen GY, Nuñez G. Sterile inflammation: sensing and reacting to damage. Nat Rev Immunol 2010; 10: 826-37.
4. Glass CK, Saijo K, Winner B, Marchetto MC, Gage FH. Mechanisms underlying inflammation in neurodegeneration. Cell 2010; 140: 918-34.
5. Chen X, Walker DG, Schmidt AM, Arancio O, Lue LF, Yan S Du. RAGE: a potential target for Abeta-mediated cellular perturbation in Alzheimer's disease. Curr Mol Med 2007; 7: 735-42.
6. Fang F, Lue LF, Yan S, et al. RAGE-dependent signaling in microglia contributes to neuroinflammation, Abeta accumulation, and impaired learning/memory in a mouse model of Alzheimer's disease. FASEB J 2010; 24: 1043-55.
7. Shaw PJ, Lamkanfi M, Kanneganti TD. NOD-like receptor (NLR) signaling beyond the inflammasome. Eur J Immunol 2010; 40: 624-7.
8. Di Virgilio F, Ceruti S, Bramanti P, Abbracchio MP. Purinergic signalling in inflammation of the central nervous system. Trends Neurosci 2009; 32: 79-87.
9. Husemann J, Loike JD, Anankov R, Febbraio M, Silverstein SC. Scavenger receptors in neurobiology and neuropathology: their role on microglia and other cells of the nervous system. Glia 2002; 40: 195-205.
10. Czeh M, Gressens P, Kaindl AM. The yin and yang of microglia. Dev Neurosci 2011; 33: 199-209.
11. Garden GA, Möller T. Microglia biology in health and disease. J Neuroimmune Pharmacol 2006; 1: 127-37.
12. Venneti S, Wiley CA, Kofler J. Imaging microglial activation during neuroinflammation and Alzheimer's disease. J Neuroimmune Pharmacol 2009; 4: 227-43.
13. Blasko I, Stampfer-Kountchev M, Robatscher P, Veerhuis R, Eikelenboom P, Grubeck-Loebenstein B. How chronic inflammation can affect the brain and support the development of Alzheimer's disease in old age: the role of microglia and astrocytes. Aging Cell 2004; 3: 169-76.
14. Arnaud L, Robakis NK, Figueiredo-Pereira ME. It may take inflammation, phosphorylation and ubiquitination to "tangle" in Alzheimer's disease. Neurodegener Dis 2006; 3: 313-9.
15. Hickman SE, Allison EK, El Khoury J. Microglial dysfunction and defective beta-amyloid clearance pathways in aging Alzheimer's disease mice. J Neurosci 2008; 28: 8354-60.
16. Rojo LE, Fernández JA, Maccioni AA, Jimenez JM, Maccioni RB. Neuroinflammation: implications for the pathogenesis and molecular diagnosis of Alzheimer's disease. Arch Med Res 2008; 39: 1-16.
17. Maccioni RB, Rojo LE, Fernández JA, Kuljis RO. The role of neuroimmunomodulation in Alzheimer's disease. Ann N Y Acad Sci2009; 1153: 240-6.
18. Eikelenboom P, van Exel E, Hoozemans JJM, Veerhuis R, Rozemuller AJM, van Gool WA. Neuroinflammation-an early event in both the history and pathogenesis of Alzheimer's disease. Neurodegener Dis 2010; 7: 38-41.
19. Green M V, Seidel J, Vaquero JJ, Jagoda E, Lee I, Eckelman WC. High resolution PET, SPECT and projection imaging in small animals. Comput Med Imaging Graph 25: 79-86.
20. Miller PW, Long NJ, Vilar R, Gee AD. Synthesis of 11C, 18F, 15O, and 13N radiolabels for positron emission tomography. Angew Chem Int Ed Engl 2008; 47: 8998-9033.
21. Evens N, Bormans GM. Non-invasive imaging of the type 2 cannabinoid receptor, focus on positron emission tomography. Curr Top Med Chem 2010; 10: 1527-43.
22. Pike VW. PET radiotracers: crossing the blood-brain barrier and surviving metabolism. Trends Pharmacol Sci 2009; 30: 431-40.
23. Serdons K, Verbruggen A, Bormans GM. Developing new molecular imaging probes for PET. Methods 2009; 48: 104-11.
24. Jaffer FA, Weissleder R. Molecular imaging in the clinical arena. JAMA 2005; 293: 855-62.
25. Chen M-K, Guilarte TR. Translocator protein 18 kDa (TSPO): molecular sensor of brain injury and repair. Pharmacol Ther 2008; 118: 1-17.
26. Cosenza-Nashat M, Zhao M-L, Suh H-S, et al. Expression of the translocator protein of 18 kDa by microglia, macrophages and astrocytes based on immunohistochemical localization in abnormal human brain. Neuropathol Appl Neurobiol 2009; 35: 306-28.
27. Mattner F, Katsifis A, Staykova M, Ballantyne P, Willenborg DO. Evaluation of a radiolabelled peripheral benzodiazepine receptor ligand in the central nervous system inflammation of experimental autoimmune encephalomyelitis: a possible probe for imaging multiple sclerosis. Eur J Nucl Med Mol Imaging 2005; 32: 557-63.
28. Venneti S, Lopresti BJ, Wiley CA. The peripheral benzodiazepine receptor (Translocator protein 18kDa) in microglia: from pathology to imaging. Prog Neurobiol 2006; 80: 308-22.
29. Converse AK, Larsen EC, Engle JW, Barnhart TE, Nickles RJ, Duncan ID. 11C-(R)-PK11195 PET imaging of microglial activation and response to minocycline in zymosan-treated rats. J Nucl Med 2011; 52: 257-62.
30. Folkersma H, Foster Dingley JC, van Berckel BNM, et al. Increased cerebral (R)-[(11)C] PK11195 uptake and glutamate release in a rat model of traumatic brain injury: a longitudinal pilot study. J Neuroinflammation 2011; 8: 67.
31. Folkersma H, Boellaard R, Yaqub M, et al. Widespread and prolonged increase in (R)-(11)C-PK11195 binding after traumatic brain injury. J Nucl Med 2011; 52: 1235-9.
32. Kumar A, Muzik O, Shandal V, Chugani D, Chakraborty P, Chugani HT. Evaluation of age-related changes in translocator protein (TSPO) in human brain using (11)C-[R]-PK11195 PET. J Neuroinflammation 2012; 9: 232.
33. Politis M, Giannetti P, Su P, et al. Increased PK11195 PET binding in the cortex of patients with MS correlates with disability. Neurology 2012; 79: 523-30.
34. Politis M, Su P, Piccini P. Imaging of microglia in patients with neurodegenerative disorders. Front Pharmacol 2012; 3: 96.
35. Gulyás B, Pavlova E, Kása P, et al. Activated MAO-B in the brain of Alzheimer patients, demonstrated by [11C]-L-deprenyl using whole hemisphere autoradiography. Neurochem Int 2011; 58: 60-8.
36. Hughes JL, Jones PS, Beech JS, et al. A microPET study of the regional distribution of [11C]-PK11195 binding following temporary focal cerebral ischemia in the rat. Correlation with post mortem mapping of microglia activation. Neuroimage 2012; 59: 2007-16.
37. Ren W, Muzik O, Jackson N, et al. Differentiation of septic and aseptic loosening by PET with both 11C-PK11195 and 18F-FDG in rat models. Nucl Med Commun 2012; 33: 747-56.
38. Rapic S, Backes H, Viel T, et al. Imaging microglial activation and glucose consumption in a mouse model of Alzheimer's disease. Neurobiol Aging 2013; 34: 351-4.
39. Garvey LJ, Pavese N, Politis M, et al. Increased microglia activation in neurologically asymptomatic HIV-infected patients receiving effective ART; An 11C-PK11195 PET study. AIDS 2013.
40. Boutin H, Prenant C, Maroy R, et al. [18F]DPA-714: direct comparison with [11C]PK11195 in a model of cerebral ischemia in rats. PLoS One 2013; 8: e56441.
41. Dickens AM, Vainio S, Marjamäki P, et al. Detection of Microglial Activation in an Acute Model of Neuroinflammation Using PET and Radiotracers 11C-(R)-PK11195 and 18F-GE-180. J Nucl Med 2014.
42. Chauveau F, Boutin H, Van Camp N, Dollé F, Tavitian B. Nuclear imaging of neuroinflammation: a comprehensive review of [11C]PK11195 challengers. Eur J Nucl Med Mol Imaging 2008; 35: 2304-19.
43. Owen DRJ, Matthews PM. Imaging brain microglial activation using positron emission tomography and translocator protein-specific radioligands. Int Rev Neurobiol 2011; 101: 19-39.
44. Venneti S, Lopresti BJ, Wang G, 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. J Neurochem 2007; 102: 2118-31.
45. Imaizumi M, Kim H-J, Zoghbi SS, et al. PET imaging with [11C]PBR28 can localize and quantify upregulated peripheral benzodiazepine receptors associated with cerebral ischemia in rat. Neurosci Lett 2007; 411: 200-5.
46. 11C]PBR28 positron emission tomography in nonhuman primates. Neuroimage 2012; 63: 232-9.
47. Briard E, Zoghbi SS, Imaizumi M, et al. Synthesis and evaluation in monkey of two sensitive 11C-labeled aryloxyanilide ligands for imaging brain peripheral benzodiazepine receptors in vivo. J Med Chem 2008; 51: 17-30.
48. Hirvonen J, Kreisl WC, Fujita M, et al. Increased in vivo expression of an inflammatory marker in temporal lobe epilepsy. J Nucl Med 2012; 53: 234-40.
49. Brown AK, Fujita M, Fujimura Y, et al. Radiation dosimetry and biodistribution in monkey and man of 11C-PBR28: a PET radioligand to image inflammation. J Nucl Med 2007; 48: 2072-9.
50. Fujita M, Imaizumi M, Zoghbi SS, 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. Neuroimage 2008; 40: 43-52.
51. Imaizumi M, Briard E, Zoghbi SS, et al. Brain and whole-body imaging in nonhuman primates of [11C]PBR28, a promising PET radioligand for peripheral benzodiazepine receptors. Neuroimage 2008; 39: 1289-98.
52. Kreisl WC, Lyoo CH, McGwier M, et al. In vivo radioligand binding to translocator protein correlates with severity of Alzheimer's disease. Brain 2013; 136: 2228-38.
53. 11C]PBR28 PET study. Brain Behav Immun 2013; 33: 131-8.
54. Wilson AA, Garcia A, Parkes J, et al. Radiosynthesis and initial evaluation of [18F]-FEPPA for PET imaging of peripheral benzodiazepine receptors. Nucl Med Biol 2008; 35: 305-14.
55. Rusjan PM, Wilson AA, Bloomfield PM, et al. Quantitation of translocator protein binding in human brain with the novel radioligand [18F]-FEPPA and positron emission tomography. J Cereb Blood Flow Metab 2011; 31: 1807-16.
56. Mizrahi R, Rusjan PM, Vitcu I, et al. Whole body biodistribution and radiation dosimetry in humans of a new PET ligand, [(18)F]-FEPPA, to image translocator protein (18 kDa). Mol Imaging Biol 2013; 15: 353-9.
57. Suridjan I, Rusjan PM, Voineskos AN, et al. Neuroinflammation in healthy aging: A PET study using a novel Translocator Protein 18kDa (TSPO) radioligand, [(18)F]-FEPPA. Neuroimage 2013; 84C: 868-75.
58. 18F]fluoro-PBR28, a novel radiotracer for imaging the TSPO 18 kDa with PET. Bioorg Med Chem Lett 2011; 21: 4819-22.
59. Moon BS, Kim BS, Park C, et al. [(18)F]Fluoromethyl-PBR28 as a Potential Radiotracer for TSPO: Preclinical Comparison with [(11)C]PBR28 in a Rat Model of Neuroinflammation. Bioconjug Chem 2014.
60. Zhang M-R, Kida T, Noguchi J, et al [(11)C]DAA1106: radiosynthesis and in vivo binding to peripheral benzodiazepine receptors in mouse brain. Nucl Med Biol 2003; 30: 513-9.
61. Zhang M-R, Maeda J, Ogawa M, et al. Development of a new radioligand, N-(5-fluoro-2-phenoxyphenyl)-N-(2-[18F]fluoroethyl-5-methoxybenzyl)acetamide, for pet imaging of peripheral benzodiazepine receptor in primate brain. J Med Chem 2004; 47: 2228-35.
62. Takano A, Piehl F, Hillert J, et al. In vivo TSPO imaging in patients with multiple sclerosis: a brain PET study with [18F]FEDAA1106. EJNMMI Res 2013; 3: 30.
63. Briard E, Hong J, Musachio JL, Zoghbi SS, Fujita M, Imaizumi M, Cropley V, Innis RB PV. Synthesis and evaluation of two candidate 11C-labeled radioligands for brain peripheral benzodiazepine receptors. J Label Compd Radiopharm 2005; 48: S4.
64. Briard E, Shah J, Musachio JL, Zoghbi SS, Fujita M, Imaizumi M, Cropley V, Innis RB PV. Synthesis and evaluation of a new 18F-labeled ligand for PET imaging of brain peripheral benzodiazepine receptors. J Label Compd Radiopharm 2005; 48: S4.
65. Imaizumi M, Briard E, Zoghbi SS, et al. Kinetic evaluation in nonhuman primates of two new PET ligands for peripheral benzodiazepine receptors in brain. Synapse 2007; 61: 595-605.
66. Lartey FM, Ahn G-O, Shen B, et al. PET Imaging of Stroke-Induced Neuroinflammation in Mice Using [(18)F]PBR06. Mol Imaging Biol 2013.
67. Fujimura Y, Zoghbi SS, Simèon FG, et al. Quantification of translocator protein (18 kDa) in the human brain with PET and a novel radioligand, (18)F-PBR06. J Nucl Med 2009; 50: 1047-53.
68. Fujimura Y, Kimura Y, Siméon FG, et al. Biodistribution and radiation dosimetry in humans of a new PET ligand, (18)F-PBR06, to image translocator protein (18 kDa). J Nucl Med 2010; 51: 145-9.
69. Dickstein LP, Zoghbi SS, Fujimura Y, et al. Comparison of 18F-and 11C-labeled aryloxyanilide analogs to measure translocator protein in human brain using positron emission tomography. Eur J Nucl Med Mol Imaging 2011; 38: 352-7.
70. James ML, Fulton RR, Vercoullie J, et al. DPA-714, a new translocator protein-specific ligand: synthesis, radiofluorination, and pharmacologic characterization. J Nucl Med 2008; 49: 814-22.
71. Chauveau F, Van Camp N, Dollé F, 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. J Nucl Med 2009; 50: 468-76.
72. Harhausen D, Sudmann V, Khojasteh U, et al. Specific imaging of inflammation with the 18 kDa translocator protein ligand DPA-714 in animal models of epilepsy and stroke. PLoS One 2013; 8: e69529.
73. Arlicot N, Vercouillie J, Ribeiro MJ, et al. Initial evaluation in healthy humans of [18F]DPA-714, a potential PET biomarker for neuroinflammation. Nucl Med Biol 2012; 39: 570-8.
74. Peyronneau M-A, Saba W, Goutal S, et al. Metabolism and quantification of [(18)F]DPA-714, a new TSPO positron emission tomography radioligand. Drug Metab Dispos 2013; 41: 122-31.
75. Corcia P, Tauber C, Vercoullie J, et al. Molecular imaging of microglial activation in amyotrophic lateral sclerosis. PLoS One 2012; 7: e52941.
76. Boutin H, Chauveau F, Thominiaux C, et al. In vivo imaging of brain lesions with [(11)C]CLINME, a new PET radioligand of peripheral benzodiazepine receptors. Glia 2007; 55: 1459-68.
77. Van Camp N, Boisgard R, Kuhnast B, et al. In vivo imaging of neuroinflammation: a comparative study between [(18)F]PBR111, [(11)C]CLINME and [(11)C]PK11195 in an acute rodent model. Eur J Nucl Med Mol Imaging 2010; 37: 962-72.
78. Fookes CJR, Pham TQ, Mattner F, et al. Synthesis and biological evaluation of substituted [18F]imidazo[1, 2-a]pyridines and [18F]pyrazolo[1, 5-a]pyrimidines for the study of the peripheral benzodiazepine receptor using positron emission tomography. J Med Chem 2008; 51: 3700-12.
79. Dedeurwaerdere S, Callaghan PD, Pham T, et al. PET imaging of brain inflammation during early epileptogenesis in a rat model of temporal lobe epilepsy. EJNMMI Res 2012; 2: 60.
80. Verschuer JD, Towson J, Eberl S, et al. Radiation dosimetry of the translocator protein ligands [18F]PBR111 and [18F]PBR102. Nucl Med Biol 2012; 39: 742-53.
81. Guo Q, Colasanti A, Owen DR, et al. Quantification of the Specific Translocator Protein Signal of 18F-PBR111 in Healthy Humans: A Genetic Polymorphism Effect on In vivo Binding. J Nucl Med 2013.
82. Chauveau F, Boutin H, Van Camp N, et al. In vivo imaging of neuroinflammation in the rodent brain with [11C]SSR180575, a novel indoleacetamide radioligand of the translocator protein (18 kDa). Eur J Nucl Med Mol Imaging 2011; 38: 509-14.
83. Vin V, Leducq N, Bono F, Herbert JM. Binding characteristics of SSR180575, a potent and selective peripheral benzodiazepine ligand. Biochem Biophys Res Commun 2003; 310: 785-90.
84. 18F]GE-180: a novel fluorine-18 labelled PET tracer for imaging Translocator protein 18 kDa (TSPO). Bioorg Med Chem Lett 2012; 22: 1308-13.
85. Owen DRJ, Gunn RN, Rabiner EA, et al. Mixed-affinity binding in humans with 18-kDa translocator protein ligands. J Nucl Med 2011; 52: 24-32.
86. Owen DR, Yeo AJ, Gunn RN, et al. An 18-kDa translocator protein (TSPO) polymorphism explains differences in binding affinity of the PET radioligand PBR28. J Cereb Blood Flow Metab 2012; 32: 1-5.
87. Doorduin J, de Vries EFJ, Dierckx RA, Klein HC. PET imaging of the peripheral benzodiazepine receptor: monitoring disease progression and therapy response in neurodegenerative disorders. Curr Pharm Des 2008; 14: 3297-315.
88. Schweitzer PJ, Fallon BA, Mann JJ, Kumar JSD. PET tracers for the peripheral benzodiazepine receptor and uses thereof. Drug Discov Today 2010; 15: 933-42.
89. Di Marzo V. The endocannabinoid system: its general strategy of action, tools for its pharmacological manipulation and potential therapeutic exploitation. Pharmacol Res 2009; 60: 77-84.
90. Lynn AB, Herkenham M. Localization of cannabinoid receptors and nonsaturable high-density cannabinoid binding sites in peripheral tissues of the rat: implications for receptor-mediated immune modulation by cannabinoids. J Pharmacol Exp Ther 1994; 268: 1612-23.
91. Galiègue S, Mary S, Marchand J, et al. Expression of central and peripheral cannabinoid receptors in human immune tissues and leukocyte subpopulations. Eur J Biochem 1995; 232: 54-61.
92. Benito C, Núñez E, Tolón RM, et al. Cannabinoid CB2 receptors and fatty acid amide hydrolase are selectively overexpressed in neuritic plaque-associated glia in Alzheimer's disease brains. J Neurosci 2003; 23: 11136-41.
93. Fernandez-Ruiz J, Gonzalez S, Romero J, Ramos J. Cannabinoids in neurodegeneration and neuroprotection. 2005.
94. Klein TW. Cannabinoid-based drugs as anti-inflammatory therapeutics. Nat Rev Immunol 2005; 5: 400-11.
95. Maresz K, Carrier EJ, Ponomarev ED, Hillard CJ, Dittel BN. Modulation of the cannabinoid CB2 receptor in microglial cells in response to inflammatory stimuli. J Neurochem 2005; 95: 437-45.
96. Steffens S, Veillard NR, Arnaud C, et al. Low dose oral cannabinoid therapy reduces progression of atherosclerosis in mice. Nature 2005; 434: 782-6.
97. Yiangou Y, Facer P, Durrenberger P, et al. COX-2, CB2 and P2X7-immunoreactivities are increased in activated microglial cells/macrophages of multiple sclerosis and amyotrophic lateral sclerosis spinal cord. BMC Neurol 2006; 6: 12.
98. Iuvone T, De Filippis D, Di Spiezio Sardo A, et al. Selective CB2 up-regulation in women affected by endometrial inflammation. J Cell Mol Med 2008; 12: 661-70.
99. Palazuelos J, Davoust N, Julien B, et al. The CB(2) cannabinoid receptor controls myeloid progenitor trafficking: involvement in the pathogenesis of an animal model of multiple sclerosis. J Biol Chem 2008; 283: 13320-9.
100. Palazuelos J, Aguado T, Pazos MR, et al. Microglial CB2 cannabinoid receptors are neuroprotective in Huntington's disease excitotoxicity. Brain 2009; 132: 3152-64.
101. Sagredo O, González S, Aroyo I, et al. Cannabinoid CB2 receptor agonists protect the striatum against malonate toxicity: relevance for Huntington's disease. Glia 2009; 57: 1154-67.
102. Weis F, Beiras-Fernandez A, Sodian R, et al. Substantially altered expression pattern of cannabinoid receptor 2 and activated endocannabinoid system in patients with severe heart failure. J Mol Cell Cardiol 2010; 48: 1187-93.
103. Martín-Moreno AM, Brera B, Spuch C, et al. Prolonged oral cannabinoid administration prevents neuroinflammation, lowers β-amyloid levels and improves cognitive performance in Tg APP 2576 mice. J Neuroinflammation 2012; 9: 8.
104. Evens N, Bosier B, Lavey BJ, et al. Labelling and biological evaluation of [(11)C]methoxy-Sch225336: a radioligand for the cannabinoid-type 2 receptor. Nucl Med Biol 2008; 35: 793-800.
105. Evens N, Muccioli GG, Houbrechts N, et al. Synthesis and biological evaluation of carbon-11-and fluorine-18-labeled 2-oxoquinoline derivatives for type 2 cannabinoid receptor positron emission tomography imaging. Nucl Med Biol 2009; 36: 455-65.
106. Vandeputte C, Evens N, Toelen J, et al. A PET brain reporter gene system based on type 2 cannabinoid receptors. J Nucl Med 2011; 52: 1102-9.
107. Evens N, Vandeputte C, Coolen C, et al. Preclinical evaluation of [11C]NE40, a type 2 cannabinoid receptor PET tracer. Nucl Med Biol 2012; 39: 389-99.
108. Turkman N, Shavrin A, Ivanov RA, et al. Fluorinated cannabinoid CB2 receptor ligands: synthesis and in vitro binding characteristics of 2-oxoquinoline derivatives. Bioorg Med Chem 2011; 19: 5698-707.
109. Turkman N, Shavrin A, Paolillo V, et al. Synthesis and preliminary evaluation of [18F]-labeled 2-oxoquinoline derivatives for PET imaging of cannabinoid CB2 receptor. Nucl Med Biol 2012; 39: 593-600.
110. Horti AG, Gao Y, Ravert HT, et al. Synthesis and biodistribution of [11C]A-836339, a new potential radioligand for PET imaging of cannabinoid type 2 receptors (CB2). Bioorg Med Chem 2010; 18: 5202-7.
111. Evens N, Vandeputte C, Muccioli GG, et al. Synthesis, in vitro and in vivo evaluation of fluorine-18 labelled FE-GW405833 as a PET tracer for type 2 cannabinoid receptor imaging. Bioorg Med Chem 2011; 19: 4499-505.
112. Fujinaga M, Kumata K, Yanamoto K, et al. Radiosynthesis of novel carbon-11-labeled triaryl ligands for cannabinoid-type 2 receptor. Bioorg Med Chem Lett 2010; 20: 1565-8.
113. Gao M, Wang M, Miller KD, Hutchins GD, Zheng Q-H. Synthesis and in vitro biological evaluation of carbon-11-labeled quinoline derivatives as new candidate PET radioligands for cannabinoid CB2 receptor imaging. Bioorg Med Chem 2010; 18: 2099-106.
114. Rühl T, Deuther-Conrad W, Fischer S, et al. Cannabinoid receptor type 2 (CB2)-selective N-aryl-oxadiazolyl-propionamides: synthesis, radiolabelling, molecular modelling and biological evaluation. Org Med Chem Lett 2012; 2: 32.
115. Teodoro R, Moldovan R-P, Lueg C, et al. Radiofluorination and biological evaluation of N-aryl-oxadiazolyl-propionamides as potential radioligands for PET imaging of cannabinoid CB2 receptors. Org Med Chem Lett 2013; 3: 11.
116. Mu L, Bieri D, Slavik R, et al. Radiolabeling and in vitro I in vivo evaluation of N-(1-adamantyl)-8-methoxy-4-oxo-1-phenyl-1, 4-dihydroquinoline-3-carboxamide as a PET probe for imaging cannabinoid type 2 receptor. J Neurochem 2013; 126: 616-24.
117. Hortala L, Arnaud J, Roux P, et al. Synthesis and preliminary evaluation of a new fluorine-18 labelled triazine derivative for PET imaging of cannabinoid CB2 receptor. Bioorg Med Chem Lett 2014; 24: 283-7.
118. Farooqui AA, Horrocks LA, Farooqui T. Modulation of inflammation in brain: a matter of fat. J Neurochem 2007; 101: 577-99.
119. McGeer PL, McGeer EG. NSAIDs and Alzheimer disease: epidemiological, animal model and clinical studies. Neurobiol Aging 2007; 28: 639-47.
120. Vlad SC, Miller DR, Kowall NW, Felson DT. Protective effects of NSAIDs on the development of Alzheimer disease. Neurology 2008; 70: 1672-7.
121. Breitner JCS, Haneuse SJPA, Walker R, et al. Risk of dementia and AD with prior exposure to NSAIDs in an elderly community-based cohort. Neurology 2009; 72: 1899-905.
122. Hernán MA, Logroscino G, García Rodriguez LA. Nonsteroidal anti-inflammatory drugs and the incidence of Parkinson disease. Neurology 2006; 66: 1097-9.
123. Wahner AD, Bronstein JM, Bordelon YM, Ritz B. Nonsteroidal anti-inflammatory drugs may protect against Parkinson disease. Neurology 2007; 69: 1836-42.
124. Esposito E, Di Matteo V, Benigno A, Pierucci M, Crescimanno G, Di Giovanni G. Non-steroidal anti-inflammatory drugs in Parkinson's disease. Exp Neurol 2007; 205: 295-312.
125. Etminan M, Carleton BC, Samii A. Non-steroidal antiinflammatory drug use and the risk of Parkinson disease: a retrospective cohort study. J Clin Neurosci 2008; 15: 576-7.
126. Bosetti F, Langenbach R, Weerasinghe GR. Prostaglandin E2 and microsomal prostaglandin E synthase-2 expression are decreased in the cyclooxygenase-2-deficient mouse brain despite compensatory induction of cyclooxygenase-1 and Ca2+-dependent phospholipase A2. J Neurochem 2004; 91: 1389-97.
127. Murakami M, Kudo I. Recent advances in molecular biology and physiology of the prostaglandin E2-biosynthetic pathway. Prog Lipid Res 2004; 43: 3-35.
128. Choi S-H, Langenbach R, Bosetti F. Cyclooxygenase-1 and-2 enzymes differentially regulate the brain upstream NF-kappa B pathway and downstream enzymes involved in prostaglandin biosynthesis. J Neurochem 2006; 98: 801-11.
129. Chandrasekharan N V, Dai H, Roos KLT, et al. COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesicIantipyretic drugs: cloning, structure, and expression. Proc Natl Acad Sci U S A 2002; 99: 13926-31.
130. Phillis JW, Horrocks LA, Farooqui AA. Cyclooxygenases, lipoxygenases, and epoxygenases in CNS: their role and involvement in neurological disorders. Brain Res Rev 2006; 52: 201-43.
131. Tzeng S-F, Hsiao H-Y, Mak O-T. Prostaglandins and cyclooxygenases in glial cells during brain inflammation. Curr Drug Targets Inflamm Allergy 2005; 4: 335-40.
132. Greenhough A, Smartt HJM, Moore AE, et al. The COX-2IPGE2 pathway: key roles in the hallmarks of cancer and adaptation to the tumour microenvironment. Carcinogenesis 2009; 30: 377-86.
133. Wang D, Dubois RN. Eicosanoids and cancer. Nat Rev Cancer 2010; 10: 181-93.
134. Rizzo MT. Cyclooxygenase-2 in oncogenesis. Clin Chim Acta 2011; 412: 671-87.
135. 18F-labeled 2, 3-diarylsubstituted indole via McMurry coupling for functional characterization of cyclooxygenase-2 (COX-2) in vitro and in vivo. Bioorg Med Chem 2012; 20: 3410-21.
136. Niwa K, Araki E, Morham SG, Ross ME, Iadecola C. Cyclooxygenase-2 contributes to functional hyperemia in whisker-barrel cortex. J Neurosci 2000; 20: 763-70.
137. Yang H, Chen C. Cyclooxygenase-2 in synaptic signaling. Curr Pharm Des 2008; 14: 1443-51.
138. Schwab JM, Beschorner R, Meyermann R, Gözalan F, Schluesener HJ. Persistent accumulation of cyclooxygenase-1-expressing microglial cells and macrophages and transient upregulation by endothelium in human brain injury. J Neurosurg 2002; 96: 892-9.
139. Pepicelli O, Fedele E, Berardi M, et al. Cyclo-oxygenase-1 and-2 differently contribute to prostaglandin E2 synthesis and lipid peroxidation after in vivo activation of N-methyl-D-aspartate receptors in rat hippocampus. J Neurochem 2005; 93: 1561-7.
140. Candelario-Jalil E, de Oliveira ACP, Gräf S, et al. Resveratrol potently reduces prostaglandin E2 production and free radical formation in lipopolysaccharide-activated primary rat microglia. J Neuroinflammation 2007; 4: 25.
141. Choi S-H, Langenbach R, Bosetti F. Genetic deletion or pharmacological inhibition of cyclooxygenase-1 attenuate lipopolysaccharide-induced inflammatory response and brain injury. FASEB J 2008; 22: 1491-501.
142. Shukuri M, Takashima-Hirano M, Tokuda K, et al. In vivo expression of cyclooxygenase-1 in activated microglia and macrophages during neuroinflammation visualized by PET with 11C-ketoprofen methyl ester. J Nucl Med 2011; 52: 1094-101.
143. Schwab JM, Nguyen TD, Postler E, Meyermann R, Schluesener HJ. Selective accumulation of cyclooxygenase-1-expressing microglial cellsImacrophages in lesions of human focal cerebral ischemia. Acta Neuropathol 2000; 99: 609-14.
144. Minghetti L. Role of COX-2 in inflammatory and degenerative brain diseases. Subcell Biochem 2007; 42: 127-41.
145. Hoozemans JJM, Rozemuller JM, van Haastert ES, Veerhuis R, Eikelenboom P. Cyclooxygenase-1 and-2 in the different stages of Alzheimer's disease pathology. Curr Pharm Des 2008; 14: 1419-27.
146. Choi S-H, Aid S, Bosetti F. The distinct roles of cyclooxygenase-1 and-2 in neuroinflammation: implications for translational research. Trends Pharmacol Sci 2009; 30: 174-81.
147. Channing M, Simpson N. Radiosynthesis of 1-[C11] polyhomoallylic fatty-acids. J Label Compd Rad 1993; 33: 541-6.
148. Rapoport SI. In vivo approaches to quantifying and imaging brain arachidonic and docosahexaenoic acid metabolism. J Pediatr 2003; 143: S26-34.
149. De Vries EFJ. Imaging of cyclooxygenase-2 (COX-2) expression: potential use in diagnosis and drug evaluation. Curr Pharm Des 2006; 12: 3847-56.
150. McCarthy TJ, Sheriff AU, Graneto MJ, Talley JJ, Welch MJ. Radiosynthesis, in vitro validation, and in vivo evaluation of 18F-labeled COX-1 and COX-2 inhibitors. J Nucl Med 2002; 43: 117-24.
151. De Vries EFJ, van Waarde A, Buursma AR, Vaalburg W. Synthesis and in vivo evaluation of 18F-desbromo-DuP-697 as a PET tracer for cyclooxygenase-2 expression. J Nucl Med 2003; 44: 1700-6.
152. Toyokuni T, Kumar JSD, Walsh JC, et al. Synthesis of 4-(5-[18F]fluoromethyl-3-phenylisoxazol-4-yl)benzenesulfonamide, a new [18F]fluorinated analogue of valdecoxib, as a potential radiotracer for imaging cyclooxygenase-2 with positron emission tomography. Bioorg Med Chem Lett 2005; 15: 4699-702.
153. Prabhakaran J, Underwood MD, Parsey R V, et al. Synthesis and in vivo evaluation of [18F]-4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide as a PET imaging probe for COX-2 expression. Bioorg Med Chem 2007; 15: 1802-7.
154. De Vries EFJ, Doorduin J, Dierckx RA, van Waarde A. Evaluation of [(11)C]rofecoxib as PET tracer for cyclooxygenase 2 overexpression in rat models of inflammation. Nucl Med Biol 2008; 35: 35-42.
155. Comley R, Passchier J, Willemsen A, et al. Uptake and regional distribution of [11C]rofecoxib in the human brain. 2010.
156. Uddin MJ, Crews BC, Ghebreselasie K, et al. Fluorinated COX-2 inhibitors as agents in PET imaging of inflammation and cancer. Cancer Prev Res (Phila) 2011; 4: 1536-45.
157. Takashima-Hirano M, Shukuri M, Takashima T, et al. General method for the (11)C-labeling of 2-arylpropionic acids and their esters: construction of a PET tracer library for a study of biological events involved in COXs expression. Chemistry 2010; 16: 4250-8.
158. Parks WC, Wilson CL, López-Boado YS. Matrix metalloproteinases as modulators of inflammation and innate immunity. Nat Rev Immunol 2004; 4: 617-29.
159. Wagner S, Breyholz H-J, Faust A, et al. Molecular imaging of matrix metalloproteinases in vivo using small molecule inhibitors for SPECT and PET. Curr Med Chem 2006; 13: 2819-38.
160. Galis ZS, Khatri JJ. Matrix metalloproteinases in vascular remodeling and atherogenesis: the good, the bad, and the ugly. Circ Res 2002; 90: 251-62.
161. Iwama S, Sugimura Y, Suzuki H, et al. Time-dependent changes in proinflammatory and neurotrophic responses of microglia and astrocytes in a rat model of osmotic demyelination syndrome. Glia 2011; 59: 452-62.
162. Siasos G, Tousoulis D, Kioufis S, et al. Inflammatory mechanisms in atherosclerosis: the impact of matrix metalloproteinases. Curr Top Med Chem 2012; 12: 1132-48.
163. Wagner S, Breyholz H-J, Law MP, et al. Novel fluorinated derivatives of the broad-spectrum MMP inhibitors N-hydroxy-2(R)-[[(4-methoxyphenyl)sulfonyl](benzyl)-and (3-picolyl)-amino]-3-methyl-butanamide as potential tools for the molecular imaging of activated MMPs with PET. J Med Chem 2007; 50: 5752-64.
164. Vos CMP, van Haastert ES, de Groot CJA, van der Valk P, de Vries HE. Matrix metalloproteinase-12 is expressed in phagocytotic macrophages in active multiple sclerosis lesions. J Neuroimmunol 2003; 138: 106-14.
165. Nuttall RK, Silva C, Hader W, et al. Metalloproteinases are enriched in microglia compared with leukocytes and they regulate cytokine levels in activated microglia. Glia 2007; 55: 516-26.
166. Dasilva AG, Yong VW. Expression and regulation of matrix metalloproteinase-12 in experimental autoimmune encephalomyelitis and by bone marrow derived macrophages in vitro. J Neuroimmunol 2008; 199: 24-34.
167. Crocker SJ, Frausto RF, Whitton JL, Milner R. A novel method to establish microglia-free astrocyte cultures: comparison of matrix metalloproteinase expression profiles in pure cultures of astrocytes and microglia. Glia 2008; 56: 1187-98.
168. Liu Y, Zhang M, Hao W, et al. Matrix metalloproteinase-12 contributes to neuroinflammation in the aged brain. Neurobiol Aging 2013; 34: 1231-9.
169. Yong VW. Metalloproteinases: mediators of pathology and regeneration in the CNS. Nat Rev Neurosci 2005; 6: 931-44.
170. Breyholz HJ, Wagner S, Levkau B, Schober O, Schäfers M, Kopka K. A 18F-radiolabeled analogue of CGS 27023A as a potential agent for assessment of matrix-metalloproteinase activity in vivo. Q J Nucl Med Mol imaging Off Publ Ital Assoc Nucl Med [and] Int Assoc Radiopharmacol (IAR), [and] Sect Soc Radiopharm 2007; 51: 24-32.
171. Breyholz H-J, Wagner S, Faust A, et al. Radiofluorinated pyrimidine-2, 4, 6-triones as molecular probes for noninvasive MMP-targeted imaging. ChemMedChem 2010; 5: 777-89.
172. Schrigten D, Breyholz H-J, Wagner S, et al. A new generation of radiofluorinated pyrimidine-2, 4, 6-triones as MMP-targeted radiotracers for positron emission tomography. J Med Chem 2012; 55: 223-32.
173. Hugenberg V, Breyholz H-J, Riemann B, et al. A new class of highly potent matrix metalloproteinase inhibitors based on triazole-substituted hydroxamates: (radio)synthesis and in vitro and first in vivo evaluation. J Med Chem 2012; 55: 4714-27.
174. Bergström M, Muhr C, Jossan S, Lilja A, Nyberg G, Långström B. Differentiation of pituitary adenoma and meningioma: visualization with positron emission tomography and [11C]-L-deprenyl. Neurosurgery 1992; 30: 855-61.
175. Fowler JS, Volkow ND, Logan J, et al. Monoamine oxidase B (MAO B) inhibitor therapy in Parkinson's disease: the degree and reversibility of human brain MAO B inhibition by Ro 19 6327. Neurology 1993; 43: 1984-92.
176. Kumlien E, Bergström M, Lilja A, et al. Positron emission tomography with [11C]deuterium-deprenyl in temporal lobe epilepsy. Epilepsia 1995; 36: 712-21.
177. Kumlien E, Nilsson A, Hagberg G, Långström B, Bergström M. PET with 11C-deuterium-deprenyl and 18F-FDG in focal epilepsy. Acta Neurol Scand 2001; 103: 360-6.
178. Fowler JS, Volkow ND, Cilento R, Wang GJ, Felder C, Logan J. Comparison of Brain Glucose Metabolism and Monoamine Oxidase B (MAO B) in Traumatic Brain Injury. Clin Positron Imaging 1999; 2: 71-9.
179. Johansson A, Engler H, Blomquist G, et al. Evidence for astrocytosis in ALS demonstrated by [11C](L)-deprenyl-D2 PET. J Neurol Sci 2007; 255: 17-22.
180. Razifar P, Axelsson J, Schneider H, Långström B, Bengtsson E, Bergström M. A new application of pre-normalized principal component analysis for improvement of image quality and clinical diagnosis in human brain PET studies--clinical brain studies using [11C]-GR205171, [11C]-L-deuterium-deprenyl, [11C]-5-Hydroxy-L-Tryptophan, [11. Neuroimage 2006; 33: 588-98.
181. Saba W, Valette H, Peyronneau M-A, et al [(11)C]SL25. 1188, a new reversible radioligand to study the monoamine oxidase type B with PET: preclinical characterisation in nonhuman primate. Synapse 2010; 64: 61-9.
182. Vasdev N, Sadovski O, Moran MD, et al. Development of new radiopharmaceuticals for imaging monoamine oxidase B. Nucl Med Biol 2011; 38: 933-43.
183. Nag S, Lehmann L, Heinrich T, et al. Synthesis of three novel fluorine-18 labeled analogues of L-deprenyl for positron emission tomography (PET) studies of monoamine oxidase B (MAO-B). J Med Chem 2011; 54: 7023-9.
184. 18F]fluorodeprenyl: a new MAO-B pet radioligand. Synapse 2012; 66: 323-30.
185. 18F]fluororasagiline, a novel positron emission tomography (PET) radioligand for monoamine oxidase B (MAO-B). Bioorg Med Chem 2012; 20: 3065-71.
186. Nag S, Kettschau G, Heinrich T, et al. Synthesis and biological evaluation of novel propargyl amines as potential fluorine-18 labeled radioligands for detection of MAO-B activity. Bioorg Med Chem 2013; 21: 186-95.
187. Monif M, Burnstock G, Williams DA. Microglia: proliferation and activation driven by the P2X7 receptor. Int J Biochem Cell Biol 2010; 42: 1753-6.
188. Skaper SD, Debetto P, Giusti P. The P2X7 purinergic receptor: from physiology to neurological disorders. FASEB J 2010; 24: 337-45.
189. Parvathenani LK, Tertyshnikova S, Greco CR, Roberts SB, Robertson B, Posmantur R. P2X7 mediates superoxide production in primary microglia and is up-regulated in a transgenic mouse model of Alzheimer's disease. J Biol Chem 2003; 278: 13309-17.
190. Romagnoli R, Baraldi PG, Cruz-Lopez O, et al. The P2X7 receptor as a therapeutic target. Expert Opin Ther Targets 2008; 12: 647-61.
191. Sanz JM, Chiozzi P, Ferrari D, et al. Activation of microglia by amyloid {beta} requires P2X7 receptor expression. J Immunol 2009; 182: 4378-85.
192. Takenouchi T, Sekiyama K, Sekigawa A, et al. P2X7 receptor signaling pathway as a therapeutic target for neurodegenerative diseases. Arch Immunol Ther Exp (Warsz) 2010; 58: 91-6.
193. Diaz-Hernandez JI, Gomez-Villafuertes R, León-Otegui M, et al. In vivo P2X7 inhibition reduces amyloid plaques in Alzheimer's disease through GSK3ß and secretases. Neurobiol Aging 2012; 33: 1816-28.
194. Honore P, Donnelly-Roberts D, Namovic MT, et al. A-740003 [N-(1-{[(cyanoimino)(5-quinolinylamino) methyl]amino}-2, 2-dimethylpropyl)-2-(3, 4-dimethoxyphenyl)acetamide], a novel and selective P2X7 receptor antagonist, dose-dependently reduces neuropathic pain in the rat. J Pharmacol Exp Ther 2006; 319: 1376-85.
195. Donnelly-Roberts DL, Jarvis MF. Discovery of P2X7 receptor-selective antagonists offers new insights into P2X7 receptor function and indicates a role in chronic pain states. Br J Pharmacol 2007; 151: 571-9.
196. Nelson DW, Gregg RJ, Kort ME, et al. Structure-activity relationship studies on a series of novel, substituted 1-benzyl-5-phenyltetrazole P2X7 antagonists. J Med Chem 2006; 49: 3659-66.
197. Carroll WA, Kalvin DM, Perez Medrano A, et al. Novel and potent 3-(2, 3-dichlorophenyl)-4-(benzyl)-4H-1, 2, 4-triazole P2X7 antagonists. Bioorg Med Chem Lett 2007; 17: 4044-8.
198. McGaraughty S, Chu KL, Namovic MT, et al. P2X7-related modulation of pathological nociception in rats. Neuroscience 2007; 146: 1817-28.
199. Florjancic AS, Peddi S, Perez-Medrano A, et al. Synthesis and in vitro activity of 1-(2, 3-dichlorophenyl)-N-(pyridin-3-ylmethyl)-1H-1, 2, 4-triazol-5-amine and 4-(2, 3-dichlorophenyl)-N-(pyridin-3-ylmethyl)-4H-1, 2, 4-triazol-3-amine P2X7 antagonists. Bioorg Med Chem Lett 2008; 18: 2089-92.
200. Gunosewoyo H, Guo JL, Bennett MR, Coster MJ, Kassiou M. Cubyl amides: novel P2X7 receptor antagonists. Bioorg Med Chem Lett 2008; 18: 3720-3.
201. Carroll WA, Donnelly-Roberts D, Jarvis MF. Selective P2X(7) receptor antagonists for chronic inflammation and pain. Purinergic Signal 2009; 5: 63-73.
202. Perez-Medrano A, Donnelly-Roberts DL, Honore P, et al. Discovery and biological evaluation of novel cyanoguanidine P2X(7) antagonists with analgesic activity in a rat model of neuropathic pain. J Med Chem 2009; 52: 3366-76.
203. Able SL, Fish RL, Bye H, et al. Receptor localization, native tissue binding and ex vivo occupancy for centrally penetrant P2X7 antagonists in the rat. Br J Pharmacol 2011; 162: 405-14.
204. Gunosewoyo H, Coster MJ, Kassiou M. Molecular probes for P2X7 receptor studies. Curr Med Chem 2007; 14: 1505-23.
205. Donnelly-Roberts DL, Namovic MT, Surber B, et al. [3H]A-804598 ([3H]2-cyano-1-[(1S)-1-phenylethyl]-3-quinolin-5-ylguanidine) is a novel, potent, and selective antagonist radioligand for P2X7 receptors. Neuropharmacology 2009; 56: 223-9.
206. Beswick PJ, Billinton A, Chambers LJ, et al. Structure-activity relationships and in vivo activity of (1H-pyrazol-4-yl)acetamide antagonists of the P2X(7) receptor. Bioorg Med Chem Lett 2010; 20: 4653-6.
207. Abberley L, Bebius A, Beswick PJ, et al. Identification of 2-oxo-N-(phenylmethyl)-4-imidazolidinecarboxamide antagonists of the P2X(7) receptor. Bioorg Med Chem Lett 2010; 20: 6370-4.
208. Abdi MH, Beswick PJ, Billinton A, et al. Discovery and structure-activity relationships of a series of pyroglutamic acid amide antagonists of the P2X7 receptor. Bioorg Med Chem Lett 2010; 20: 5080-4.
209. Gleave RJ, Walter DS, Beswick PJ, et al. Synthesis and biological activity of a series of tetrasubstituted-imidazoles as P2X(7) antagonists. Bioorg Med Chem Lett 2010; 20: 4951-4.
210. Matasi JJ, Brumfield S, Tulshian D, et al. Synthesis and SAR development of novel P2X7 receptor antagonists for the treatment of pain: part 1. Bioorg Med Chem Lett 2011; 21: 3805-8.
211. Duplantier AJ, Dombroski MA, Subramanyam C, et al. Optimization of the physicochemical and pharmacokinetic attributes in a 6-azauracil series of P2X7 receptor antagonists leading to the discovery of the clinical candidate CE-224, 535. Bioorg Med Chem Lett 2011; 21: 3708-11.
212. 7 receptor. Bioorg Med Chem Lett 2011; 21: 5475-9.
213. Brumfield S, Matasi JJ, Tulshian D, et al. Synthesis and SAR development of novel P2X7 receptor antagonists for the treatment of pain: part 2. Bioorg Med Chem Lett 2011; 21: 7287-90.
214. Lee GE, Lee W-G, Lee S-Y, et al. Characterization of protoberberine analogs employed as novel human P2X7 receptor antagonists. Toxicol Appl Pharmacol 2011; 252: 192-200.
215. Lee W-G, Lee S-D, Cho J-H, et al. Structure-activity relationships and optimization of 3, 5-dichloropyridine derivatives as novel P2X(7) receptor antagonists. J Med Chem 2012; 55: 3687-98.
216. Letavic MA, Lord B, Bischoff F, et al. Synthesis and Pharmacological Characterization of Two Novel, Brain Penetrating P2X 7 Antagonists. ACS Med Chem Lett 2013; 4: 419-22.
217. Bhattacharya A, Wang Q, Ao H, et al. Pharmacological characterization of a novel centrally permeable P2X7 receptor antagonist: JNJ-47965567. Br J Pharmacol 2013; 170: 624-40.
218. Guile SD, Alcaraz L, Birkinshaw TN, et al. Antagonists of the P2X(7) receptor. From lead identification to drug development. J Med Chem 2009; 52: 3123-41.
219. Gunosewoyo H, Kassiou M. P2X purinergic receptor ligands: recently patented compounds. Expert Opin Ther Pat 2010; 20: 625-46.
220. Akdis CA, Simons FER. Histamine receptors are hot in immunopharmacology. Eur J Pharmacol 2006; 533: 69-76.
221. Parsons ME, Ganellin CR. Histamine and its receptors. Br J Pharmacol 2006; 147 Suppl S127-35.
222. Celanire S, Wijtmans M, Talaga P, Leurs R, de Esch IJP. Keynote review: histamine H3 receptor antagonists reach out for the clinic. Drug Discov Today 2005; 10: 1613-27.
223. Esbenshade TA, Browman KE, Bitner RS, Strakhova M, Cowart MD, Brioni JD. The histamine H3 receptor: an attractive target for the treatment of cognitive disorders. Br J Pharmacol 2008; 154: 1166-81.
224. Leurs R, Chazot PL, Shenton FC, Lim HD, de Esch IJP. Molecular and biochemical pharmacology of the histamine H4 receptor. Br J Pharmacol 2009; 157: 14-23.
225. Zampeli E, Tiligada E. The role of histamine H4 receptor in immune and inflammatory disorders. Br J Pharmacol 2009; 157: 24-33.
226. Strakhova MI, Cuff CA, Manelli AM, et al. In vitro and in vivo characterization of A-940894: a potent histamine H4 receptor antagonist with anti-inflammatory properties. Br J Pharmacol 2009; 157: 44-54.
227. Sander K, Kottke T, Proschak E, et al. Lead identification and optimization of diaminopyrimidines as histamine H4 receptor ligands. Inflamm Res 2010; 59 Suppl 2: S249-51.
228. Savall BM, Gomez L, Chavez F, et al. Tricyclic aminopyrimidine histamine H4 receptor antagonists. Bioorg Med Chem Lett 2011; 21: 6577-81.
229. Mowbray CE, Bell AS, Clarke NP, et al. Challenges of drug discovery in novel target space. The discovery and evaluation of PF-3893787: a novel histamine H4 receptor antagonist. Bioorg Med Chem Lett 2011; 21: 6596-602.
230. Lane CAL, Hay D, Mowbray CE, et al. Synthesis of novel histamine H4 receptor antagonists. Bioorg Med Chem Lett 2012; 22: 1156-9.
231. Funke U, Vugts DJ, Janssen B, et al. (11) C-labeled and (18) F-labeled PET ligands for subtype-specific imaging of histamine receptors in the brain. J Labelled Comp Radiopharm 2013; 56: 120-9.