Positron emission tomography imaging of the 18-kDa translocator protein (TSPO) with [18F]FEMPA in Alzheimer’s disease patients and control subjects

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• 作者：Andrea Varrone ; Vesa Oikonen ; Anton Forsberg…
• 关键词：Neuroinflammation ; Microglia ; Translocator protein ; Dementia ; Alzheimer
• 刊名：European Journal of Nuclear Medicine and Molecular Imaging
• 出版年：2015
• 出版时间：March 2015
• 年：2015
• 卷：42
• 期：3
• 页码：438-446
• 全文大小：1,778 KB
• 参考文献：1. Wyss-Coray T, Rogers J. Inflammation in Alzheimer disease -a brief review of the basic science and clinical literature. Cold Spring Harb Perspect Med. 2012;2:a006346. CrossRef
  2. Rupprecht R, Papadopoulos V, Rammes G, Baghai TC, Fan J, Akula N, et al. Translocator protein (18 kDa) (TSPO) as a therapeutic target for neurological and psychiatric disorders. Nat Rev Drug Discov. 2010;9:971-8. CrossRef
  3. Scarf AM, Kassiou M. The translocator protein. J Nucl Med. 2011;52:677-0. CrossRef
  4. Bird JL, Izquierdo-Garcia D, Davies JR, Rudd JH, Probst KC, Figg N, et al. Evaluation of translocator protein quantification as a tool for characterising macrophage burden in human carotid atherosclerosis. Atherosclerosis. 2010;210:388-1. CrossRef
  5. Cosenza-Nashat M, Zhao ML, Suh HS, Morgan J, Natividad R, Morgello 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;35:306-8. CrossRef
  6. Kuhlmann AC, Guilarte TR. Cellular and subcellular localization of peripheral benzodiazepine receptors after trimethyltin neurotoxicity. J Neurochem. 2000;74:1694-04. CrossRef
  7. Venneti S, Lopresti BJ, Wiley CA. Molecular imaging of microglia/macrophages in the brain. Glia. 2013;61:10-3. CrossRef
  8. Cagnin A, Brooks DJ, Kennedy AM, Gunn RN, Myers R, Turkheimer FE, et al. In-vivo measurement of activated microglia in dementia. Lancet. 2001;358:461-. CrossRef
  9. Edison P, Archer HA, Gerhard A, Hinz R, Pavese N, Turkheimer FE, et al. Microglia, amyloid, and cognition in Alzheimer’s disease: an [11C](R)PK11195-PET and [11C]PIB-PET study. Neurobiol Dis. 2008;32:412-. CrossRef
  10. 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-. CrossRef
  11. 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;34:128-6. CrossRef
  12. Dolle F, Luus C, Reynolds A, Kassiou M. Radiolabelled molecules for imaging the translocator protein (18 kDa) using positron emission tomography. Curr Med Chem. 2009;16:2899-23. CrossRef
  13. Yasuno F, Ota M, Kosaka J, Ito H, Higuchi M, Doronbekov TK, et al. Increased binding of peripheral benzodiazepine receptor in Alzheimer’s disease measured by positron emission tomography with [11C]DAA1106. Biol Psychiatry. 2008;64:835-1. CrossRef
  14. Yasuno F, Kosaka J, Ota M, Higuchi M, Ito H, Fujimura Y, et al. Increased binding of peripheral benzodiazepine receptor in mild cognitive impairment-dementia converters measured by positron emission tomography with [11C]DAA1106. Psychiatry Res. 2012;203:67-4. CrossRef
  15. Varrone A, Mattsson P, Forsberg A, Takano A, Nag S, Gulyas B, 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. Eur J Nucl Med Mol Imag
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Nuclear Medicine
  Imaging and Radiology
  Orthopedics
  Cardiology
  Oncology
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1619-7089

文摘

Purpose Imaging of the 18-kDa translocator protein (TSPO) is a potential tool for examining microglial activation and neuroinflammation in early Alzheimer’s disease (AD). [18F]FEMPA is a novel high-affinity second-generation TSPO radioligand that has displayed suitable pharmacokinetic properties in preclinical studies. The aims of this study were to quantify the binding of [18F]FEMPA to TSPO in AD patients and controls and to investigate whether higher [18F]FEMPA binding in AD patients than in controls could be detected in vivo. Methods Ten AD patients (five men, five women; age 66.9?±-.3 years; MMSE score 25.5?±-.5) and seven controls (three men, four women; age 63.7?±-.2 years, MMSE score 29.3?±-.0) were studied using [18F]FEMPA at Turku (13 subjects) and at Karolinska Institutet (4 subjects). The in vitro binding affinity for TSPO was assessed using PBR28 in a competition assay with [3H]PK11195 in seven controls and eight?AD patients. Cortical and subcortical regions of interest were examined. Quantification was performed using a two-tissue compartment model (2TCM) and Logan graphical analysis (GA). The outcome measure was the total distribution volume (V T). Repeated measures analysis of variance was used to assess the effect of group and TSPO binding status on V T. Results Five AD patients and four controls were high-affinity binders (HABs). Three AD patients and three controls were mixed-affinity binders. V T estimated with Logan GA was significantly correlated with V T estimated with the 2TCM in both controls (r--.97) and AD patients (r--.98) and was selected for the final analysis. Significantly higher V T was found in the medial temporal cortex in AD patients than in controls (p--.044) if the TSPO binding status was entered as a covariate. If only HABs were included, significantly higher V T?was found in the medial and lateral temporal cortex, posterior cingulate, caudate, putamen, thalamus and cerebellum in AD patients than in controls (p--.05). Conclusion [18F]FEMPA seems to be a suitable radioligand for detecting increased TSPO binding in AD patients if their binding status is taken into account.