title: Age and disease related changes in the translocator protein (TSPO) system in the human brain: positron emission tomography measurements with [11C]vinpocetine.
abstract: OBJECTIVE
  The main objectives of the present study were (i) to measure density changes of activated microglia and the peripheral benzodiazepine receptor/translocator protein (TSPO) system during normal ageing in the human brain with positron emission tomography (PET) using the TSPO molecular imaging biomarker [(11)C]vinpocetine and (ii) to compare the level and pattern of TSPO in Alzheimer (AD) patients with age matched healthy subjects, in order to assess the biomarker's usefulness as a diagnostic imaging marker in normal (ageing) and pathological (AD) up-regulation of microglia.
  
  
  METHODS
  PET measurements were made in healthy volunteers, aged between 25 and 78 years, and AD patients, aged between 67 and 82 years, using [(11)C]vinpocetine as the tracer. Global and regional quantitative parameters of tracer uptake and binding, including time activity curves (TAC) of standard uptake values (%SUV), binding affinity parameters, intensity spectrum and homogeneity of the uptake distribution were measured and analysed.
  
  
  RESULTS
  Both %SUV and binding values increased with age linearly in the whole brain and in all brain regions. There were no significant differences between the %SUV values of the AD patients and age matched control subjects. There were, however, significant differences in %SUV values in a large number of brain regions between young subjects and old subjects, as well as young subjects and AD patients. The intensity spectrum analysis and homogeneity analysis of the voxel data show that the homogeneity of the %SUV values decreases with ageing and during the disease, whereas the centre of the intensity spectrum is shifted to higher %SUV values. These data indicate an inhomogeneous up-regulation of the TSPO system during ageing and AD. These changes were significant between the group of young subjects and old subjects, as well as young subjects and AD patients, but not between old subjects and AD patients.
  
  
  CONCLUSIONS
  The present data indicate that [(11)C]vinpocetine may serve as a molecular imaging biomarker of the activity of the TSPO system and, consequently, of the up-regulation of microglia during ageing and in neuroinflammatory diseases. However, the global and regional brain %SUV values between AD patients and age matched controls are not different from each other. The disease specific changes, measured with [(11)C]vinpocetine in AD, are significantly different from those measured in age matched controls only if the inhomogeneities in the uptake pattern are explored with advanced mathematical techniques. For this reason, PET studies using [(11)C]vinpocetine, as molecular imaging biomarker, can efficiently visualise the activation of microglia and the up-regulation of TSPO during ageing and in diseased brains with the help of an appropriate inhomogeneity analysis of the radioligand's brain uptake pattern.
authors.affiliation: Karolinska Institutet, Department of Clinical Neuroscience, Centrum for Psychiatry Research, Stockholm, Sweden. balazs.gulyas@ki.se
authors.forename: Balázs
authors.initials: B
authors.lastname: Gulyás
authors.forename: Adám
authors.initials: A
authors.lastname: Vas
authors.forename: Miklós
authors.initials: M
authors.lastname: Tóth
authors.forename: Akihiro
authors.initials: A
authors.lastname: Takano
authors.forename: Andrea
authors.initials: A
authors.lastname: Varrone
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Cselényi
authors.forename: Martin
authors.initials: M
authors.lastname: Schain
authors.forename: Patrik
authors.initials: P
authors.lastname: Mattsson
authors.forename: Christer
authors.initials: C
authors.lastname: Halldin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D003627:Data Interpretation, Statistical; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007553:Isotope Labeling; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D018079:Receptors, GABA / Q000378:metabolism*; D014748:Vinca Alkaloids
chemical_list: D019275:Radiopharmaceuticals; D018079:Receptors, GABA; C499229:TSPO protein, human; D014748:Vinca Alkaloids; C013983:vinpocetine