Mapping neuroinflammation in frontotemporal dementia with molecular PET imaging

Journal of Neuroinflammation

Volumn 12, Issue 1, 2015, Pages

  Zhang, Jing ^a  

^a UNIVERSITY OF WESTERN ONTARIO   (Canada)

Author keywords

Frontotemporal dementia; Microglia; Molecular imaging; Neuroinflammation; Translocator protein

Indexed keywords

DAA1106 C11; DPA 714 F18; FEDAA1106 F18; FEPPA F18; MEMBRANE PROTEIN; N SEC BUTYL 1 (2 CHLOROPHENYL) N METHYL 3 ISOQUINOLINECARBOXAMIDE C 11; PBR06 F18; RADIOPHARMACEUTICAL AGENT; TRANSLOCATOR PROTEIN; UNCLASSIFIED DRUG;

BINDING AFFINITY; CELL ACTIVATION; FRONTAL CORTEX; FRONTOTEMPORAL DEMENTIA; HUMAN; MICROGLIA; NERVOUS SYSTEM INFLAMMATION; NEUROIMAGING; NONHUMAN; POSITRON EMISSION TOMOGRAPHY; REVIEW; BRAIN MAPPING; COMPLICATION; DIAGNOSTIC IMAGING; ENCEPHALITIS; METABOLISM; PATHOLOGY;

BRAIN MAPPING; ENCEPHALITIS; FRONTOTEMPORAL DEMENTIA; HUMANS; POSITRON-EMISSION TOMOGRAPHY; RADIOPHARMACEUTICALS;

EID: 84931271049     PISSN: None     EISSN: 17422094     Source Type: Journal    
DOI: 10.1186/s12974-015-0236-5     Document Type: Review

References (93)

1. Neary D, Snowden JS, Mann DMA. Frontotemporal lobar degeneration: clinical and pathological relationships. Acta Neuropathol. 2007;114:31-8.
2. Hodges JR, Davies R, Xuereb J, Kril J, Halliday G. Survival in frontotemporal dementia. Neurology. 2003;61(3):349-54.
3. Riedl L, Mackenzie IR, Förstl H, Kurz A, Diehl-Schmid J. Frontotemporal lobar degeneration: current perspectives. Neuropsychiatric Disease Treatment. 2014;10:297-310.
4. Rademakers R, Neumann M, Mackenzie IR. Advances in understanding the molecular basis of frontotemporal dementia. Nat Rev Neurol. 2012;8(8):423-34.
5. Diehl-Schmid J, Pohl C, Perneczky R, Hartmann J, Förstl H, Kurz A. Frühsymptome, Überlebenszeit und Todesursachen. Initial symptoms, survival and causes of death in 115 patients with frontotemporal lobar degeneration. Fortschr Neurol Psychiatr. 2007;75(12):708-13.
6. Womack KB, Diaz-Arrastia R, Aizenstein HJ, Arnold SE, Barbas NR, Boeve BF, et al. Temporoparietal hypometabolism in frontotemporal lobar degeneration and associated imaging diagnostic errors. Arch Neurol. 2011;68(3):329-37.
7. Ho SW, Tsui YT, Wong TT, Cheung SK, Goggins WB, Yi LM, et al. Effects of 17-allylamino-17-demethoxygeldanamycin (17-AAG) in transgenic mouse models of frontotemporal lobar degeneration and Alzheimer's disease. Transl Neurodegener. 2013;2(1):24.
8. Neumann K, Farias G, Slachevsky A, Perez P, Maccioni RB. Human platelets tau: a potential peripheral marker for Alzheimer's disease. J Alzheimers Dis. 2011;25:103-9.
9. Borza LR. A review on the cause-effect relationship between oxidative stress and toxic proteins in the pathogenesis of neurodegenerative diseases. Rev Med Chir Soc Med Nat Iasi. 2014;118(1):19-27.
10. Heneka MT, Kummer MP, Latz E. Innate immune activation in neurodegenerative disease. Nat Rev Immunol. 2014;14(7):463-77.
11. Morales I, Guzmán-Martínez L, Cerda-Troncoso C, Farías GA, Maccioni RB. Neuroinflammation in the pathogenesis of Alzheimer's disease. A rational framework for the search of novel therapeutic approaches. Front Cell Neurosci. 2014;8:112.
12. Birch AM, Katsouri L, Sastre M. Modulation of inflammation in transgenic models of Alzheimer's disease. J Neuroinflammation. 2014;11:25-38.
13. Miller ZA, Rankin KP, Graff-Radford NR, Takada LT, Sturm VE, Cleveland CM, et al. TDP-43 frontotemporal lobar degeneration and autoimmune disease. J Neurol Neurosurg Psychiatry. 2013;84(9):956-62.
14. Jacobs AH, Tavitian B. INMiND consortium. Noninvasive molecular imaging of neuroinflammation. J Cereb Blood Flow Metab. 2012;32(7):1393-415.
15. Venneti S, Wiley CA, Kofler J. Imaging microglial activation during neuroinflammation and Alzheimer's disease. J Neuroimmune Pharmacol. 2009;4(2):227-43.
16. Kleinberger G, Capell A, Haass C, Van Broeckhoven C. Mechanisms of granulin deficiency: lessons from cellular and animal models. Mol Neurobiol. 2013;47:337-60.
17. Nichol KE, Kim R, Cotman CW. Bcl-2 family protein behaviour in frontotemporal dementia implies vascular involvement. Neurology. 2001;56(11 Suppl 4):S35-40.
18. Pickford F, Marcus J, Camargo LM, Xiao Q, Graham D, Mo JR, et al. Progranulin is a chemoattractant for microglia and stimulates their endocytic activity. Am J Pathol. 2011;178:284-95.
19. Rosso S, Landweer E, Houterman M, Donker Kaat L, van Duijn CM, van Swieten JC. Medical and environmental risk factors for sporadic frontotemporal dementia: a retrospective case-control study. J Neurol Neurosurg Psychiatry. 2003;74:1574-6.
20. Sjögren M, Folkesson S, Blennow K, Tarkowski E. Increased intrathecal inflammatory activity in frontotemporal dementia: pathophysiological implications. J Neurol Neurosurg Psychiatry. 2004;75:1107-11.
21. Cagnin A, Kassiou M, Meikle SR, Banati RB. In vivo evidence for microglial activation in neurodegenerative dementia. Acta Neurol Scand. 2006;114 Suppl 185:107-14.
22. Okello A, Koivunen J, Edison P, Archer HA, Turkheimer FE, Någren K, et al. Conversion of amyloid positive and negative MCI to AD over 3 years: an 11C-PIB PET study. Neurology. 2009;73(10):754-60.
23. Bhaskar K, Konerth M, Kokiko-Cochran ON, Cardona A, Ransohoff RM, Lamb BT. Regulation of tau pathology by the microglial fractalkine receptor. Neuron. 2010;68:19-31.
24. 11C]DAA1106. Psychiatry Res. 2012;203(1):67-74.
25. Yoshiyama Y, Higuchi M, Zhang B, Huang SM, Iwata N, Saido TC. Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model. Neuron. 2007;53:337-51.
26. Zimmer ER, Leuzy A, Benedet AL, Breitner J, Gauthier S, Rosa-Net P. Tracking neuroinflammation in Alzheimer's disease: the role of positron emission tomography imaging. J Neuroinflammation. 2014;11:120.
27. Henry CJ, Huang Y, Wynne AM, Godbout JP. Peripheral lipopolysaccharide (LPS) challenge promotes microglial hyperactivity in aged mice that is associated with exaggerated induction of both pro-inflammatory IL-1beta and anti-inflammatory IL-10 cytokines. Brain Behav Immun. 2009;23(3):309-17.
28. Hommet C, Mondon K, Camus V, Ribeiro MJ, Beaufils E, Arlicot N, et al. Neuroinflammation and β amyloid deposition in Alzheimer's disease: in vivo quantification with molecular imaging. Dement Geriatr Cogn Disord. 2014;37(1-2):1-18.
29. Guerreiro RJ, Lohmann E, Brás JM, Gibbs JR, Rohrer JD, Gurunlian N, et al. Using exome sequencing to reveal mutations in TREM2 presenting as a frontotemporal dementia-like syndrome without bone involvement. JAMA Neurol. 2013;70:78-84.
30. Rayaprolu S, Mullen B, Baker M, Lynch T, Finger E, Seeley WW, et al. TREM2 in neurodegeneration: evidence for association of the p.R47H variant with frontotemporal dementia and Parkinson's disease. Mol Neurodegener. 2013;8:19.
31. Prinz M, Priller J. Microglia and brain macrophages in the molecular age: from origin to neuropsychiatric disease. Nat Rev Neurosci. 2014;15(5):300-12.
32. Liberatore GT, Jackson-Lewis V, Vukosavic S, Mandir AS, Vila M, McAuliffe WG, et al. Inducible nitric oxide synthase stimulates dopaminergic neurodegeneration in the MPTP model of Parkinson disease. Nat Med. 1999;5:1403-9.
33. McGeer PL, McGeer EG. Inflammation and the degenerative diseases of aging. Ann N Y Acad Sci. 2004;1035:104-16.
34. Kitazawa M, Oddo S, Yamasaki TR, Green KN, LaFerla FM. Lipopolysaccharide-induced inflammation exacerbates tau pathology by a cyclin-dependent kinase 5-mediated pathway in a transgenic model of Alzheimer's disease. J Neurosci. 2005;25:8843-53.
35. Cagnin A, Rossor M, Sampson EL, Mackinnon T, Banati RB. In vivo detection of microglial activation in frontotemporal dementia. Ann Neurol. 2004;56:894-7.
36. Venneti S, Wang G, Nguyen J, Wiley CA. The positron emission tomography ligand DAA1106 binds with high affinity to activated microglia in human neurological disorders. J Neuropathol Exp Neurol. 2008;67:1001-10.
37. Lant SB, Robinson AC, Thompson JC, Rollinson S, Pickering-Brown S, Snowden JS, et al. Patterns of microglial cell activation in frontotemporal lobar degeneration. Neuropathol Appl Neurobiol. 2014;40(6):686-96.
38. Wiley CA, Lopresti BJ, Venneti S, Price J, Klunk WE, DeKosky ST, et al. Carbon 11-labeled Pittsburgh compound B and carbon 11-labeled (R)-PK11195 positron emission tomographic imaging in Alzheimer disease. Arch Neurol. 2009;66:60-7.
39. Schuitemaker A, Kropholler MA, Boellaard R, van der Flier WM, Kloet RW, van der Doef TF, et al. Microglial activation in Alzheimer's disease: an (R) [11C]PK11195 positron emission tomography study. Neurobiol Aging. 2013;34:128-36.
40. Chauveau F, Van Camp N, Dollé F, Kuhnast B, Hinnen F, Damont A, 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(3):468-76.
41. Van Camp N, Boisgard R, Kuhnast B, Thézé B, Viel T, Grégoire MC, 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(5):962-72.
42. Vas A, Shchukin Y, Karrenbauer VD, Cselényi Z, Kostulas K, Hillert J, et al. Functional neuroimaging in multiple sclerosis with radiolabelled glia markers: preliminary comparative PET studies with [11C]vinpocetine and [11C]PK11195 in patients. J Neurol Sci. 2008;264(1-2):9-17.
43. Miyoshi M, Shinotoh H, Wszolek ZK, Strongosky AJ, Shimada H, Arakawa R, et al. In vivo detection of neuropathologic changes in presymptomatic MAPT mutation carriers: a PET and MRI study. Parkinsonism Relat Disord. 2010;16(6):404-8.
44. Kreisl WC, Lyoo CH, McGwier M, Snow J, Jenko KJ, Kimura N, et al. Biomarkers Consortium PET Radioligand Project Team. In vivo radioligand binding to translocator protein correlates with severity of Alzheimer's disease. Brain. 2013;136(Pt 7):2228-38.
45. Oh U, Fujita M, Ikonomidou VN, Evangelou IE, Matsuura E, Harberts E, et al. Translocator protein PET imaging for glial activation in multiple sclerosis. J Neuroimmune Pharmacol. 2011;6(3):354-61.
46. Fujita M, Imaizumi M, Zoghbi SS, Fujimura Y, Farris AG, Suhara T, 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(1):43-52.
47. Owen DR, Gunn RN, Rabiner EA, Bennacef I, Fujita M, Kreisl WC, et al. Mixed-affinity binding in humans with 18-kDa translocator protein ligands. J Nucl Med. 2011;52(1):24-32.
48. Owen DR, Howell OW, Tang SP, Wells LA, Bennacef I, Bergstrom M, et al. Two binding sites for [3H]PBR28 in human brain: implications for TSPO PET imaging of neuroinflammation. J Cereb Blood Flow Metab. 2010;30(9):1608-18.
49. Mizrahi R, Rusjan PM, Kennedy J, Pollock B, Mulsant B, Suridjan I, et al. Translocator protein (18 kDa) polymorphism (rs6971) explains in-vivo brain binding affinity of the PET radioligand [(18)F]-FEPPA. J Cereb Blood Flow Metab. 2012;32(6):968-72.
50. Owen DR, Yeo AJ, Gunn RN, Song K, Wadsworth G, Lewis A, 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):1-5.
51. Varrone A, Mattsson P, Forsberg A, Takano A, Nag S, Gulyás B, et al. In vivo imaging of the 18-kDa translocator protein (TSPO) with [18 F]FEDAA1106 and PET does not show increased binding in Alzheimer's disease patients. Eur J Nucl Med Mol Imaging. 2013;40(6):921-31.
52. Takano A, Piehl F, Hillert J, Varrone A, Nag S, Gulyás B, et al. In vivo TSPO imaging in patients with multiple sclerosis: a brain PET study with [18 F]FEDAA1106. EJNMMI Res. 2013;3(1):30.
53. Fujimura Y, Zoghbi SS, Simeon FG, Taku A, Pike VW, Innis RB, et al. Quantification of translocator protein (18 kDa) in the human brain with PET and a novel radioligand, 18F-PBR06. J Nucl Med. 2009;50:1047-53.
54. Wilson AA, Garcia A, Parkes J, McCormick P, Stephenson KA, Houle S, et al. Radiosynthesis and initial evaluation of [18F]-FEPPA for PET imaging of peripheral benzodiazepine receptors. Nucl Med Biol. 2008;35(3):305-14.
55. James ML, Fulton RR, Vercoullie J, Henderson DJ, Garreau L, Chalon S, et al. DPA-714, a new translocator protein-specific ligand: synthesis, radiofluorination, and pharmacologic characterization. J Nucl Med. 2008;49:814-22.
56. Arlicot N, Vercouillie J, Ribeiro MJ, Tauber C, Venel Y, Baulieu JL, et al. Initial evaluation in healthy humans of [18F]DPA-714, a potential PET biomarker for neuroinflammation. Nucl Med Biol. 2012;39(4):570-8.
57. Hatano K, Yamada T, Toyama H, Kudo G, Nomura M, Suzuki H, et al. Correlation between FEPPA uptake and microglia activation in 6-OHDA injured rat brain. Neuroimage. 2010;52 Suppl 1:S138-8.
58. Liu F, Zhang X, Patterson TA, Liu S, Ali SF, Paule MG, et al. Assessment of potential neuronal toxicity of inhaled anesthetics in the developing nonhuman primate. J Drug Alcohol Res. 2012;1:1-9.
59. Zhang X, Paule MG, Newport GD, Liu F, Callicott R, Liu S, et al. MicroPET/CT imaging of [18F]-FEPPA in the nonhuman primate: a potential biomarker of pathogenic processes associated with anesthetic-induced neurotoxicity. ISRN Anesthesiology. 2012;261640:11.
60. Zhang X, Liu S, Paule MG, Newport GD, Callicott R, Berridge MS, et al. Protective effects of acetyl L-carnitine on inhalation anesthetic-induced neuronal damage in the nonhuman primate. J Mol Pharm Org Process Res. 2013;1:1.
61. Bennacef I, Salinas C, Horvath G, Gunn R, Bonasera T, Wilson A, et al. Comparison of [11C]PBR28 and [18F]FEPPA as CNS peripheral benzodiazepine receptor PET ligands in the pig. J Nucl Med. 2008;49(Supplement 1):81P.
62. Vasdev N, Green DE, Vines DC, McLarty K, McCormick PN, Moran MD, et al. Positron-emission tomography imaging of the TSPO with [(18)F]FEPPA in a preclinical breast cancer model. Cancer Biother Radiopharm. 2013;28(3):254-9.
63. Jennings D, Evaluation of [18F] FEPPA and PET imaging as a marker of inflammation in subjects with neurological conditions, [Clinical Trial: http://clinicaltrials.gov/show/NCT00970333 ], 2009-2012.
64. Rusjan PM, Wilson AA, Bloomfield PM, Vitcu I, Meyer JH, Houle S, 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(8):1807-16.
65. Suridjan I, Rusjan PM, Kenk M, Verhoeff NP, Voineskos AN, Rotenberg D, et al. Quantitative imaging of neuroinflammation in human white matter: a positron emission tomography study with translocator protein 18 kDa radioligand, [18F]-FEPPA. Synapse. 2014;68(11):536-47.
66. Suridjan I, Rusjan PM, Voineskos AN, Selvanathan T, Setiawan E, Strafella AP, et al. Neuroinflammation in healthy aging: a PET study using a novel translocator protein 18 kDa (TSPO) radioligand, [(18)F]-FEPPA. Neuroimage. 2014;1(84):868-75.
67. Suridjan I, Pollock BG, Voineskos AN, Verhoeff P, Chow T, Mulsant BH, Rusjan PM, Houle S, Mizrahi R. Mapping neuroinflammation in vivo in healthy aging and Alzheimer's disease: a PET study using a novel translocator protein 18kDA (TSPO) radioligand, [18F]-FEPPA, 2012. (poster), Alzheimer's & Dementia, 8(4), Suppl 693:P4-164
68. Suridjan I, Pollock BG, Voineskos AN, Verhoeff P, Chow T, Mulsant BH, Rusjan PM, Houle S, Mizrahi R. Mapping neuroinflammation in-vivo in Alzheimer's disease: a PET study using a novel TSPO radioligand, [18F]FEPPA. 39th Annual Harvey Stancer Research Day, University of Toronto, Toronto, 2013 (poster).
69. Koshimori Y, Ko JH, Mizrahi R, Rusjan PM, Wilson AA, Houle S, et al. Activated microglia in Parkinson's disease: a PET study with a novel radiotracer, 18FFEPPA [abstract]. Mov Disord. 2012;27 Suppl 1:741.
70. Ko JH, Koshimori Y, Mizrahi R, Rusjan P, Wilson AA, Lang AE, et al. Voxel-based imaging of translocator protein 18 kDa (TSPO) in high-resolution PET. J Cereb Blood Flow Metab. 2013;33(3):348-50.
71. Bernards N, Pottier G, Thézé B, Dollé F, Boisgard R. In vivo evaluation of inflammatory bowel disease with the aid of μPET and the translocator protein 18 kDa radioligand [18F]DPA-714. Mol Imaging Biol. 2015;17:67-75.
72. Wu C, Yue X, Lang L, Kiesewetter DO, Li F, Zhu Z, et al. Longitudinal PET imaging of muscular inflammation using 18F-DPA-714 and 18F-Alfatide II and differentiation with tumors. Theranostics. 2014;4(5):546-55.
73. Doorduin J, Klein HC, Dierckx RA, James M, Kassiou M, de Vries EF. [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. Mol Imaging Biol. 2009;11(6):386-98.
74. Boutin H, Prenant C, Maroy R, Galea J, Greenhalgh AD, Smigova A, et al. [18F]DPA-714: direct comparison with [11C]PK11195 in a model of cerebral ischemia in rats. PLoS One. 2013;8(2):e56441.
75. Awde AR, Boisgard R, Thézé B, Dubois A, Zheng J, Dollé F, et al. The translocator protein radioligand 18F-DPA-714 monitors antitumor effect of erufosine in a rat 9L intracranial glioma model. J Nucl Med. 2013;54(12):2125-31.
76. Pottier G, Bernards N, Dollé F, Boisgard R. [18F]DPA-714 as a biomarker for positron emission tomography imaging of rheumatoid arthritis in an animal model. Arthritis Res Ther. 2014;16(2):R69.
77. Gent YY, Weijers K, Molthoff CF, Windhorst AD, Huisman MC, Kassiou M, 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. Arthritis Res Ther. 2014;16(2):R70.
78. Corcia P, Tauber C, Vercoullie J, Arlicot N, Prunier C, Praline J, et al. Molecular imaging of microglial activation in amyotrophic lateral sclerosis. PLoS One. 2012;7(12):e52941.
79. Ribeiro MJ, Vercouillie J, Debiais S, Cottier JP, Bonnaud I, Camus V, et al. Could (18) F-DPA-714 PET imaging be interesting to use in the early post-stroke period? EJNMMI Res. 2014;4:28.
80. Mizrahi R, Rusjan PM, Vitcu I, Ng A, Wilson AA, Houle S, 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(3):353-9.
81. Farde L, Hall H, Ehrin E, Sedvall G. Quantitative analysis of D2 dopamine receptor binding in the living human brain by PET. Science. 1986;231(4735):258-61.
82. Lammertsma AA, Bench CJ, Hume SP, Osman S, Gunn K, Brooks DJ, et al. Comparison of methods for analysis of clinical [11C]raclopride studies. J Cereb Blood Flow Metab. 1996;16(1):42-52.
83. Lammertsma AA, Hume SP. Simplified reference tissue model for PET receptor studies. Neuroimage. 1996;4(3 Pt 1):153-8.
84. Logan J, Fowler JS, Volkow ND, Wang GJ, Ding YS, Alexoff DL. Distribution volume ratios without blood sampling from graphical analysis of PET data. J Cereb Blood Flow Metab. 1996;16(5):834-40.
85. Ichise M, Liow JS, Lu JQ, Takano A, Model K, Toyama H, et al. Linearized reference tissue parametric imaging methods: application to [11C]DASB positron emission tomography studies of the serotonin transporter in human brain. J Cereb Blood Flow Metab. 2003;23(9):1096-112.
86. Csele'nyi Z, Olsson H, Halldin C, Gulya's B, Farde L. A comparison of recent parametric neuroreceptor mapping approaches based on measurements with the high affinity PET radioligands [11C]FLB 457 and [11C]WAY 100635. Neuroimage. 2006;32(4):1690-708.
87. Turkheimer FE, Edison P, Pavese N, Roncaroli F, Anderson AN, Hammers A, et al. Reference and target region modeling of [11C]-(R)-PK11195 brain studies. J Nucl Med. 2007;48:158-67.
88. Rizzo G, Veronese M, Tonietto M, Zanotti-Fregonara P, Turkheimer FE, Bertoldo A. Kinetic modeling without accounting for the vascular component impairs the quantification of [(11)C]PBR28 brain PET data. J Cereb Blood Flow Metab. 2014;34(6):1060-9.
89. Mizrahi R, 2012. Imaging neuroinflammation in mild cognitive impairment using a novel translocator protein 18kDA (TSPO) PET radioligand: [18F]-FEPPA. [Research Project] http://westonbraininstitute.ca/funded-research/projects/imaging-neuroinflammation-mild-cognitive-impairment-using-novel-translocator-protein-18kda-tspo-pet-radioligand-18f-feppa/ . Accessed 20 June 2014.
90. Mizrahi R, 2012. F-18-FEPPA: a novel in-vivo molecular biomarker of neuroinflammation in Alzheimer's disease. [Research Project] http://www.alzheimer.ca/en/algoma/Research/Alzheimer-Society-Research-Program/Alzheimer-Society-Research-Program/ASRP-Award-recipients-2012/Biomedical-grants . Accessed 20 June 2014.
91. Strafella A. 2012. Can neuroinflammation be used as a biomarker for Parkinson's disease? [Research project] http://westonbraininstitute.ca/funded-research/projects/can-neuroinflammation-used-biomarker-parkinsons-disease/ . Accessed 20 June 2014.
92. Innis RB, PET Evaluation of brain peripheral benzodiazepine receptors using [11C]PBR28 in frontotemporal dementia. [Clinical Trial: http://clinicaltrials.gov/show/NCT00613119 ], 2008-2014.
93. Hommet C, PET imaging of the translocator proteine ligands (TSPO) with [18F] DPA-714 biomarker of neuroinflammation in cognitive decline (NIDECO). [Clinical Trial: http://clinicaltrials.gov/show/NCT02062099 ], 2014.