Neuro-PET – ein Update

Leonie Beyer; Axel Rominger

doi:10.1055/a-0621-3227

Der Nuklearmediziner, Inhaltsverzeichnis

Der Nuklearmediziner 2018; 41(03): 253-263
DOI: 10.1055/a-0621-3227

PET Update 2018

Neuro-PET – ein Update

Neuro-PET - an update

Leonie Beyer

¹Klinik und Poliklinik für Nuklearmedizin, Klinikum der Universität München, München

,

Axel Rominger

²Klinik für Nuklearmedizin, Inselspital, Universität Bern, Bern, Schweiz

› Institutsangaben

Abstract

Zusammenfassung

Neurologische Fragestellungen haben in der Positronen-Emissions-Tomografie seit vielen Jahren einen festen Stellenwert. In dieser Übersichtsarbeit werden in der Klinik gängige Untersuchungsmethoden bei der Demenzdiagnostik, Abklärung von Bewegungsstörungen sowie der Epilepsiediagnostik unter Berücksichtigung aktueller Leitlinien dargestellt und durch aktuelle Entwicklungen in der Wissenschaft erweitert. Ebenso wird die nuklearmedizinische Diagnostik von Hirntumoren samt theragnostischem Ausblick aufgezeigt. In einem weiteren Subkapitel wird die Entwicklung im Bereich der Neuroinflammation erläutert. Insgesamt lässt sich festhalten, dass in der Neuronuklearmedizin in den letzten Jahren einige Neuentwicklungen hervorgebracht wurden, welche sicherlich ihren Stellenwert auch in der klinischen Routine finden werden.

Abstract

Neurological investigations have an established role in positron-emission-tomography for many years. In this review, clinical routine PET procedures will be presented for diagnoses related to dementia, movement disorders and epilepsy, taking into consideration the current guidelines. Furthermore latest findings and ongoing research will be presented. Complemented by the diagnostics of brain tumors including theragnostic aspects the paper will finalize with latest developments in the field of neuroinflammation. In summary, there have been several new developments in neuro-PET in recent years, which will find their role in future clinical routine.

Schlüsselwörter

Positronen-Emissions-Tomographie - Neurodegeneration - Neuroonkologie - Neuroinflammation - Epilepsie - Radiotracer

Keywords

positron-emission-tomography - neurodegeneration - neurooncology - neuroinflammation - epilepsy - radiotracer

Volltext

Referenzen

Literatur
1 Kotzerke J, Oehme L, Lindner O. et al. [Positron emission tomography 2008 in Germany - results of the query and current status]. Nuklearmedizin Nuclear medicine 2010; 49: 58-64
2 Kotzerke J, Oehme L, Grosse J. et al. [Positron emission tomography 2013 in Germany. Results of the query and current status]. Nuklearmedizin Nuclear medicine 2015; 54: 53-59
3 Dilling H. Internationale Klassifikation psychischer Störungen: ICD-10 Kapitel V (F) – Klinisch-diagnostische Leitlinien. Huber Hans; 2015
4 McKhann GM, Knopman DS, Chertkow H. et al. The diagnosis of dementia due to Alzheimerʼs disease: recommendations from the National Institute on Aging-Alzheimerʼs Association workgroups on diagnostic guidelines for Alzheimerʼs disease. Alzheimers Dement 2011; 7: 263-269
5 Dubois B, Feldman HH, Jacova C. et al. Advancing research diagnostic criteria for Alzheimerʼs disease: the IWG-2 criteria. The Lancet Neurology 2014; 13: 614-629
6 Leitlinie Demenzen, Entwicklungsstufe S3, 2016. Deutsche Gesellschaft für Psychiatrie und Psychotherapie, Psychosomatik und Nervenheilkunde e.V. (DGPPN), Deutsche Gesellschaft für Neurologie (DGN). 2016
7 Jack Jr CR, Bennett DA, Blennow K. et al. A/T/N: An unbiased descriptive classification scheme for Alzheimer disease biomarkers. Neurology 2016; 87: 539-547
8 Burdette JH, Minoshima S, VanderBorght T. et al. Alzheimer disease: improved visual interpretation of PET images by using three-dimensional stereotaxic surface projections. Radiology 1996; 198: 837-843
9 Minoshima S, Frey KA, Koeppe RA. et al. A diagnostic approach in Alzheimerʼs disease using three-dimensional stereotactic surface projections of fluorine-18-FDG PET. J Nucl Med 1995; 36: 1238-1248
10 Bloudek LM, Spackman DE, Blankenburg M. et al. Review and meta-analysis of biomarkers and diagnostic imaging in Alzheimerʼs disease. Journal of Alzheimerʼs disease: JAD 2011; 26: 627-645
11 Foster NL, Heidebrink JL, Clark CM. et al. FDG-PET improves accuracy in distinguishing frontotemporal dementia and Alzheimerʼs disease. Brain: a journal of neurology 2007; 130: 2616-2635
12 Klunk WE, Engler H, Nordberg A. et al. Imaging brain amyloid in Alzheimerʼs disease with Pittsburgh Compound-B. Ann Neurol 2004; 55: 306-319
13 Villemagne VL, Mulligan RS, Pejoska S. et al. Comparison of 11C-PiB and 18F-florbetaben for Abeta imaging in ageing and Alzheimerʼs disease. Eur J Nucl Med Mol Imaging 2012; 39: 983-989
14 Sabri O, Sabbagh MN, Seibyl J. et al. Florbetaben PET imaging to detect amyloid beta plaques in Alzheimerʼs disease: phase 3 study. Alzheimers Dement 2015; 11: 964-974
15 Ikonomovic MD, Buckley CJ, Heurling K. et al. Post-mortem histopathology underlying beta-amyloid PET imaging following flutemetamol F 18 injection. Acta neuropathologica communications 2016; 4: 130
16 Clark CM, Pontecorvo MJ, Beach TG. et al. Cerebral PET with florbetapir compared with neuropathology at autopsy for detection of neuritic amyloid-beta plaques: a prospective cohort study. Lancet Neurol 2012; 11: 669-678
17 Clark CM, Schneider JA, Bedell BJ. et al. Use of florbetapir-PET for imaging beta-amyloid pathology. JAMA 2011; 305: 275-283
18 Jack Jr CR, Wiste HJ, Weigand SD. et al. Age-specific population frequencies of cerebral beta-amyloidosis and neurodegeneration among people with normal cognitive function aged 50-89 years: a cross-sectional study. The Lancet Neurology 2014; 13: 997-1005
19 Johnson KA, Minoshima S, Bohnen NI. et al. Appropriate use criteria for amyloid PET: a report of the Amyloid Imaging Task Force, the Society of Nuclear Medicine and Molecular Imaging, and the Alzheimerʼs Association. Alzheimerʼs & dementia: the journal of the Alzheimerʼs Association 2013; 9: e1-16
20 Jessen F, Spottke A, Boecker H. et al. Design and first baseline data of the DZNE multicenter observational study on predementia Alzheimerʼs disease (DELCODE). Alzheimerʼs research & therapy 2018; 10: 15
21 Budd Haeberlein S, OʼGorman J, Chiao P. et al. Clinical Development of Aducanumab, an Anti-Abeta Human Monoclonal Antibody Being Investigated for the Treatment of Early Alzheimerʼs Disease. The journal of prevention of Alzheimerʼs disease 2017; 4: 255-263
22 Brendel M, Schnabel J, Schonecker S. et al. Additive value of amyloid-PET in routine cases of clinical dementia work-up after FDG-PET. European journal of nuclear medicine and molecular imaging 2017; 44: 2239-2248
23 Barthel H, Sabri O. Clinical Use and Utility of Amyloid Imaging. Journal of nuclear medicine: official publication, Society of Nuclear Medicine 2017; 58: 1711-1717
24 Hsiao IT, Huang CC, Hsieh CJ. et al. Perfusion-like template and standardized normalization-based brain image analysis using 18F-florbetapir (AV-45/Amyvid) PET. European journal of nuclear medicine and molecular imaging 2013; 40: 908-920
25 Daerr S, Brendel M, Zach C. et al. Evaluation of early-phase [18F]-florbetaben PET acquisition in clinical routine cases. NeuroImage Clinical 2017; 14: 77-86
26 Tiepolt S, Hesse S, Patt M. et al. Early [(18)F]florbetaben and [(11)C]PiB PET images are a surrogate biomarker of neuronal injury in Alzheimerʼs disease. Eur J Nucl Med Mol Imaging 2016; 43: 1700-1709
27 Meyer PT, Hellwig S, Amtage F. et al. Dual-biomarker imaging of regional cerebral amyloid load and neuronal activity in dementia with PET and 11C-labeled Pittsburgh compound B. J Nucl Med 2011; 52: 393-400
28 Drzezga A, Barthel H, Minoshima S. et al. Potential Clinical Applications of PET/MR Imaging in Neurodegenerative Diseases. Journal of nuclear medicine: official publication, Society of Nuclear Medicine 2014; 55 (Suppl. 02) 47S-55S
29 Barthel H, Schroeter ML, Hoffmann KT. et al. PET/MR in dementia and other neurodegenerative diseases. Seminars in nuclear medicine 2015; 45: 224-233
30 Werner P, Rullmann M, Bresch A. et al. Impact of attenuation correction on clinical [(18)F]FDG brain PET in combined PET/MRI. EJNMMI research 2016; 6: 47
31 Cecchin D, Palombit A, Castellaro M. et al. Brain PET and functional MRI: why simultaneously using hybrid PET/MR systems?. The quarterly journal of nuclear medicine and molecular imaging: official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the So 2017; 61: 345-359
32 Eggert KM. Leitlinie Parkinson-Syndrome – Diagnostik und Therapie, Entwicklungsstufe S2k, 2012. Deutsche Gesellschaft für Neurologie.
33 Levin J, Kurz A, Arzberger T. et al. The Differential Diagnosis and Treatment of Atypical Parkinsonism. Deutsches Ärzteblatt international 2016; 113: 61-69
34 Schreckenberger M, Hagele S, Siessmeier T. et al. The dopamine D2 receptor ligand 18F-desmethoxyfallypride: an appropriate fluorinated PET tracer for the differential diagnosis of parkinsonism. Eur J Nucl Med Mol Imaging 2004; 31: 1128-1135
35 Hellwig S, Amtage F, Kreft A. et al. [(1)(8)F]FDG-PET is superior to [(1)(2)(3)I]IBZM-SPECT for the differential diagnosis of parkinsonism. Neurology 2012; 79: 1314-1322
36 Mille E, Levin J, Brendel M. et al. Cerebral Glucose Metabolism and Dopaminergic Function in Patients with Corticobasal Syndrome. Journal of neuroimaging: official journal of the American Society of Neuroimaging 2017; 27: 255-261
37 Gilman S. Functional imaging with positron emission tomography in multiple system atrophy. Journal of neural transmission (Vienna, Austria: 1996) 2005; 112: 1647-1655
38 Amtage F, Maurer C, Hellwig S. et al. Functional correlates of vertical gaze palsy and other ocular motor deficits in PSP: an FDG-PET study. Parkinsonism & related disorders 2014; 20: 898-906
39 Kikuchi A, Okamura N, Hasegawa T. et al. In vivo visualization of tau deposits in corticobasal syndrome by 18F-THK5351 PET. Neurology 2016; 87: 2309-2316
40 Coakeley S, Cho SS, Koshimori Y. et al. Positron emission tomography imaging of tau pathology in progressive supranuclear palsy. Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism 2017; 37: 3150-3160
41 Whitwell JL, Lowe VJ, Tosakulwong N. et al. [18 F]AV-1451 tau positron emission tomography in progressive supranuclear palsy. Movement disorders: official journal of the Movement Disorder Society 2017; 32: 124-133
42 Kantarci K, Lowe VJ, Boeve BF. et al. AV-1451 tau and beta-amyloid positron emission tomography imaging in dementia with Lewy bodies. Annals of neurology 2017; 81: 58-67
43 Smith R, Scholl M, Widner H. et al. In vivo retention of 18F-AV-1451 in corticobasal syndrome. Neurology 2017; 89: 845-853
44 Brendel M, Schonecker S, Hoglinger G. et al. [(18)F]-THK5351 PET Correlates with Topology and Symptom Severity in Progressive Supranuclear Palsy. Front Aging Neurosci 2017; 9: 440
45 Harada R, Okamura N, Furumoto S. et al. 18F-THK5351: A Novel PET Radiotracer for Imaging Neurofibrillary Pathology in Alzheimer Disease. J Nucl Med 2016; 57: 208-214
46 Chien DT, Bahri S, Szardenings AK. et al. Early clinical PET imaging results with the novel PHF-tau radioligand [F-18]-T807. Journal of Alzheimerʼs disease: JAD 2013; 34: 457-468
47 Ng KP, Pascoal TA, Mathotaarachchi S. et al. Monoamine oxidase B inhibitor, selegiline, reduces 18F-THK5351 uptake in the human brain. Alzheimerʼs research & therapy 2017; 9: 25
48 Lemoine L, Gillberg PG, Svedberg M. et al. Comparative binding properties of the tau PET tracers THK5117, THK5351, PBB3, and T807 in postmortem Alzheimer brains. Alzheimerʼs research & therapy 2017; 9: 96
49 Gokdemir S, Halac M, Albayram S. et al. Contribution of FDG-PET in epilepsy surgery: consistency and postoperative results compared with magnetic resonance imaging and electroencephalography. Turkish neurosurgery 2015; 25: 53-57
50 Fei P, Soucy JP, Obaid S. et al. The Value of Regional Cerebral Blood Flow SPECT and FDG PET in Operculoinsular Epilepsy. Clinical nuclear medicine 2018; 43: e67-e73
51 Hodolic M, Topakian R, Pichler R. (18)F-fluorodeoxyglucose and (18)F-flumazenil positron emission tomography in patients with refractory epilepsy. Radiology and oncology 2016; 50: 247-253
52 Savic I, Ingvar M, Stone-Elander S. Comparison of [11C]flumazenil and [18F]FDG as PET markers of epileptic foci. Journal of neurology, neurosurgery, and psychiatry 1993; 56: 615-621
53 Mitterhauser M, Wadsak W, Wabnegger L. et al. Biological evaluation of 2ʼ-[18F]fluoroflumazenil ([18F]FFMZ), a potential GABA receptor ligand for PET. Nuclear medicine and biology 2004; 31: 291-295
54 Rathore C, Dickson JC, Teotonio R. et al. The utility of 18F-fluorodeoxyglucose PET (FDG PET) in epilepsy surgery. Epilepsy research 2014; 108: 1306-1314
55 Scott JN, Brasher PM, Sevick RJ. et al. How often are nonenhancing supratentorial gliomas malignant? A population study. Neurology 2002; 59: 947-949
56 Ostrom QT, Gittleman H, Liao P. et al. CBTRUS Statistical Report: Primary brain and other central nervous system tumors diagnosed in the United States in 2010-2014. Neuro-oncology 2017; 19 (Suppl. 05) v1-v88
57 la Fougere C, Suchorska B, Bartenstein P. et al. Molecular imaging of gliomas with PET: opportunities and limitations. Neuro-oncology 2011; 13: 806-819
58 Thomas DG, Beaney RP, Brooks DJ. Positron emission tomography in the study of cerebral tumours. Neurosurgical review 1984; 7: 253-258
59 Ericson K, Lilja A, Bergstrom M. et al. Positron emission tomography with ([11C]methyl)-L-methionine, [11C]D-glucose, and [68Ga]EDTA in supratentorial tumors. Journal of computer assisted tomography 1985; 9: 683-689
60 Heiss WD, Wienhard K, Wagner R. et al. F-Dopa as an amino acid tracer to detect brain tumors. Journal of nuclear medicine: official publication, Society of Nuclear Medicine 1996; 37: 1180-1182
61 Albert NL, Weller M, Suchorska B. et al. Response Assessment in Neuro-Oncology working group and European Association for Neuro-Oncology recommendations for the clinical use of PET imaging in gliomas. Neuro-oncology 2016; 18: 1199-1208
62 Rapp M, Heinzel A, Galldiks N. et al. Diagnostic performance of 18F-FET PET in newly diagnosed cerebral lesions suggestive of glioma. Journal of nuclear medicine: official publication, Society of Nuclear Medicine 2013; 54: 229-235
63 Hutterer M, Nowosielski M, Putzer D. et al. [18F]-fluoro-ethyl-L-tyrosine PET: a valuable diagnostic tool in neuro-oncology, but not all that glitters is glioma. Neuro-oncology 2013; 15: 341-351
64 Dunet V, Pomoni A, Hottinger A. et al. Performance of 18F-FET versus 18F-FDG-PET for the diagnosis and grading of brain tumors: systematic review and meta-analysis. Neuro-oncology 2016; 18: 426-434
65 Jansen NL, Graute V, Armbruster L. et al. MRI-suspected low-grade glioma: is there a need to perform dynamic FET PET?. European journal of nuclear medicine and molecular imaging 2012; 39: 1021-1029
66 Pafundi DH, Laack NN, Youland RS. et al. Biopsy validation of 18F-DOPA PET and biodistribution in gliomas for neurosurgical planning and radiotherapy target delineation: results of a prospective pilot study. Neuro-oncology 2013; 15: 1058-1067
67 Grosu AL, Weber WA, Riedel E. et al. L-(methyl-11C) methionine positron emission tomography for target delineation in resected high-grade gliomas before radiotherapy. International journal of radiation oncology, biology, physics 2005; 63: 64-74
68 Suchorska B, Jansen NL, Linn J. et al. Biological tumor volume in 18FET-PET before radiochemotherapy correlates with survival in GBM. Neurology 2015; 84: 710-719
69 Ewelt C, Floeth FW, Felsberg J. et al. Finding the anaplastic focus in diffuse gliomas: the value of Gd-DTPA enhanced MRI, FET-PET, and intraoperative, ALA-derived tissue fluorescence. Clinical neurology and neurosurgery 2011; 113: 541-547
70 Kumar AJ, Leeds NE, Fuller GN. et al. Malignant gliomas: MR imaging spectrum of radiation therapy- and chemotherapy-induced necrosis of the brain after treatment. Radiology 2000; 217: 377-384
71 Galldiks N, Dunkl V, Stoffels G. et al. Diagnosis of pseudoprogression in patients with glioblastoma using O-(2-[18F]fluoroethyl)-L-tyrosine PET. European journal of nuclear medicine and molecular imaging 2015; 42: 685-695
72 Galldiks N, Stoffels G, Filss C. et al. The use of dynamic O-(2-18F-fluoroethyl)-l-tyrosine PET in the diagnosis of patients with progressive and recurrent glioma. Neuro-oncology 2015; 17: 1293-1300
73 Wyss M, Hofer S, Bruehlmeier M. et al. Early metabolic responses in temozolomide treated low-grade glioma patients. Journal of neuro-oncology 2009; 95: 87-93
74 Colavolpe C, Chinot O, Metellus P. et al. FDG-PET predicts survival in recurrent high-grade gliomas treated with bevacizumab and irinotecan. Neuro-oncology 2012; 14: 649-657
75 Singhal T, Narayanan TK, Jacobs MP. et al. 11C-methionine PET for grading and prognostication in gliomas: a comparison study with 18F-FDG PET and contrast enhancement on MRI. Journal of nuclear medicine: official publication, Society of Nuclear Medicine 2012; 53: 1709-1715
76 Jansen NL, Suchorska B, Wenter V. et al. Dynamic 18F-FET PET in newly diagnosed astrocytic low-grade glioma identifies high-risk patients. Journal of nuclear medicine: official publication, Society of Nuclear Medicine 2014; 55: 198-203
77 Galldiks N, Stoffels G, Filss CP. et al. Role of O-(2-(18)F-fluoroethyl)-L-tyrosine PET for differentiation of local recurrent brain metastasis from radiation necrosis. Journal of nuclear medicine: official publication, Society of Nuclear Medicine 2012; 53: 1367-1374
78 Glaudemans AW, Enting RH, Heesters MA. et al. Value of 11C-methionine PET in imaging brain tumours and metastases. European journal of nuclear medicine and molecular imaging 2013; 40: 615-635
79 Louis DN, Perry A, Reifenberger G. et al. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta neuropathologica 2016; 131: 803-820
80 Goldbrunner R, Minniti G, Preusser M. et al. EANO guidelines for the diagnosis and treatment of meningiomas. The Lancet Oncology 2016; 17: e383-391
81 Dutour A, Kumar U, Panetta R. et al. Expression of somatostatin receptor subtypes in human brain tumors. International journal of cancer 1998; 76: 620-627
82 Reubi JC, Maurer R, Klijn JG. et al. High incidence of somatostatin receptors in human meningiomas: biochemical characterization. The Journal of clinical endocrinology and metabolism 1986; 63: 433-438
83 Rachinger W, Stoecklein VM, Terpolilli NA. et al. Increased 68Ga-DOTATATE uptake in PET imaging discriminates meningioma and tumor-free tissue. Journal of nuclear medicine: official publication, Society of Nuclear Medicine 2015; 56: 347-353
84 Afshar-Oromieh A, Giesel FL, Linhart HG. et al. Detection of cranial meningiomas: comparison of (6)(8)Ga-DOTATOC PET/CT and contrast-enhanced MRI. European journal of nuclear medicine and molecular imaging 2012; 39: 1409-1415
85 Chatalic KL, Kwekkeboom DJ, de Jong M. Radiopeptides for Imaging and Therapy: A Radiant Future. Journal of nuclear medicine: official publication, Society of Nuclear Medicine 2015; 56: 1809-1812
86 Seystahl K, Stoecklein V, Schuller U. et al. Somatostatin receptor-targeted radionuclide therapy for progressive meningioma: benefit linked to 68Ga-DOTATATE/-TOC uptake. Neuro-oncology 2016; 18: 1538-1547
87 Unterrainer M, Niyazi M, Ruf V. et al. The endothelial prostate-specific membrane antigen is highly expressed in gliosarcoma and visualized by [68Ga]-PSMA-11 PET: a theranostic outlook for brain tumor patients?. Neuro-oncology 2017; 19: 1698-1699
88 Albrecht DS, Granziera C, Hooker JM. et al. In Vivo Imaging of Human Neuroinflammation. ACS chemical neuroscience 2016; 7: 470-483
89 Feeney C, Scott G, Raffel J. et al. Kinetic analysis of the translocator protein positron emission tomography ligand [(18)F]GE-180 in the human brain. European journal of nuclear medicine and molecular imaging 2016; 43: 2201-2210
90 Liu GJ, Middleton RJ, Hatty CR. et al. The 18 kDa translocator protein, microglia and neuroinflammation. Brain pathology (Zurich, Switzerland) 2014; 24: 631-653
91 Tu LN, Morohaku K, Manna PR. et al. Peripheral benzodiazepine receptor/translocator protein global knock-out mice are viable with no effects on steroid hormone biosynthesis. The Journal of biological chemistry 2014; 289: 27444-27454
92 Turkheimer FE, Rizzo G, Bloomfield PS. et al. The methodology of TSPO imaging with positron emission tomography. Biochemical Society transactions 2015; 43: 586-592
93 Wadsworth H, Jones PA, Chau WF. et al. [(1)(8)F]GE-180: a novel fluorine-18 labelled PET tracer for imaging Translocator protein 18 kDa (TSPO). Bioorganic & medicinal chemistry letters 2012; 22: 1308-1313
94 Vomacka L, Albert NL, Lindner S. et al. TSPO imaging using the novel PET ligand [(18)F]GE-180: quantification approaches in patients with multiple sclerosis. EJNMMI research 2017; 7: 89
95 Albert NL, Unterrainer M, Fleischmann DF. et al. TSPO PET for glioma imaging using the novel ligand (18)F-GE-180: first results in patients with glioblastoma. European journal of nuclear medicine and molecular imaging 2017; 44: 2230-2238
96 Heneka MT, Carson MJ, El Khoury J. et al. Neuroinflammation in Alzheimerʼs disease. The Lancet Neurology 2015; 14: 388-405
97 Brendel M, Focke C, Blume T. et al. Time Courses of Cortical Glucose Metabolism and Microglial Activity Across the Life Span of Wild-Type Mice: A PET Study. Journal of nuclear medicine: official publication, Society of Nuclear Medicine 2017; 58: 1984-1990
98 Brendel M, Kleinberger G, Probst F. et al. Increase of TREM2 during Aging of an Alzheimerʼs Disease Mouse Model Is Paralleled by Microglial Activation and Amyloidosis. Frontiers in aging neuroscience 2017; 9: 8
99 Brendel M, Probst F, Jaworska A. et al. Glial Activation and Glucose Metabolism in a Transgenic Amyloid Mouse Model: A Triple-Tracer PET Study. Journal of nuclear medicine: official publication, Society of Nuclear Medicine 2016; 57: 954-960
100 Kreisl WC, Henter ID, Innis RB. Imaging Translocator Protein as a Biomarker of Neuroinflammation in Dementia. Advances in pharmacology (San Diego, Calif) 2018; 82: 163-185
101 Stefaniak J, OʼBrien J. Imaging of neuroinflammation in dementia: a review. Journal of neurology, neurosurgery, and psychiatry 2016; 87: 21-28
102 Spillantini MG. Parkinsonʼs disease, dementia with Lewy bodies and multiple system atrophy are alpha-synucleinopathies. Parkinsonism & related disorders 1999; 5: 157-162
103 Spires-Jones TL, Attems J, Thal DR. Interactions of pathological proteins in neurodegenerative diseases. Acta neuropathologica 2017; 134: 187-205
104 Fodero-Tavoletti MT, Mulligan RS, Okamura N. et al. In vitro characterisation of BF227 binding to alpha-synuclein/Lewy bodies. European journal of pharmacology 2009; 617: 54-58
105 Kikuchi A, Takeda A, Okamura N. et al. In vivo visualization of alpha-synuclein deposition by carbon-11-labelled 2-[2-(2-dimethylaminothiazol-5-yl)ethenyl]-6-[2-(fluoro)ethoxy]benzoxazole positron emission tomography in multiple system atrophy. Brain: a journal of neurology 2010; 133: 1772-1778
106 Zhang X, Jin H, Padakanti PK. et al. Radiosynthesis and in Vivo Evaluation of Two PET Radioligands for Imaging alpha-Synuclein. Applied sciences (Basel, Switzerland) 2014; 4: 66-78
107 Chu W, Zhou D, Gaba V. et al. Design, Synthesis, and Characterization of 3-(Benzylidene)indolin-2-one Derivatives as Ligands for alpha-Synuclein Fibrils. Journal of medicinal chemistry 2015; 58: 6002-6017
108 Gao J, Wang L, Huntley ML. et al. Pathomechanisms of TDP-43 in neurodegeneration. Journal of neurochemistry