title: Low background and high contrast PET imaging of amyloid-β with [11C]AZD2995 and [11C]AZD2184 in Alzheimer's disease patients.
abstract: OBJECTIVE
  The aim of this study was to evaluate AZD2995 side by side with AZD2184 as novel PET radioligands for imaging of amyloid-β in Alzheimer's disease (AD).
  
  
  METHODS
  In vitro binding of tritium-labelled AZD2995 and AZD2184 was studied and compared with that of the established amyloid-β PET radioligand PIB. Subsequently, a first-in-human in vivo PET study was performed using [(11)C]AZD2995 and [(11)C]AZD2184 in three healthy control subjects and seven AD patients.
  
  
  RESULTS
  AZD2995, AZD2184 and PIB were found to share the same binding site to amyloid-β. [(3)H]AZD2995 had the highest signal-to-background ratio in brain tissue from patients with AD as well as in transgenic mice. However, [(11)C]AZD2184 had superior imaging properties in PET, as shown by larger effect sizes comparing binding potential values in cortical regions of AD patients and healthy controls. Nevertheless, probably due to a lower amount of nonspecific binding, the group separation of the distribution volume ratio values of [(11)C]AZD2995 was greater in areas with lower amyloid-β load, e.g. the hippocampus.
  
  
  CONCLUSIONS
  Both AZD2995 and AZD2184 detect amyloid-β with high affinity and specificity and also display a lower degree of nonspecific binding than that reported for PIB. Overall [(11)C]AZD2184 seems to be an amyloid-β radioligand with higher uptake and better group separation when compared to [(11)C]AZD2995. However, the very low nonspecific binding of [(11)C]AZD2995 makes this radioligand potentially interesting as a tool to study minute levels of amyloid-β. This sensitivity may be important in investigating, for example, early prodromal stages of AD or in the longitudinal study of a disease modifying therapy.
authors: Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. anton.forsberg@ki.se
authors: Anton
authors: A
authors: Forsberg
authors: Anders
authors: A
authors: Juréus
authors: Zsolt
authors: Z
authors: Cselényi
authors: Maria
authors: M
authors: Eriksdotter
authors: Yvonne
authors: Y
authors: Freund-Levi
authors: Fredrik
authors: F
authors: Jeppsson
authors: Britt-Marie
authors: BM
authors: Swahn
authors: Johan
authors: J
authors: Sandell
authors: Per
authors: P
authors: Julin
authors: Magnus
authors: M
authors: Schou
authors: Jan
authors: J
authors: Andersson
authors: Peter
authors: P
authors: Johnström
authors: Katarina
authors: K
authors: Varnäs
authors: Christer
authors: C
authors: Halldin
authors: Lars
authors: L
authors: Farde
authors: Samuel
authors: S
authors: Svensson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000235:genetics; D000631:Aminopyridines / Q000493:pharmacokinetics; D016229:Amyloid beta-Peptides / Q000032:analysis*; D000814:Aniline Compounds; D000818:Animals; D052160:Benzothiazoles / Q000493:pharmacokinetics; D001583:Benzoxazoles / Q000493:pharmacokinetics; D001665:Binding Sites; D001921:Brain / Q000000981:diagnostic imaging; D002250:Carbon Radioisotopes; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D049268:Positron-Emission Tomography; D011485:Protein Binding; D011869:Radioligand Assay; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D012680:Sensitivity and Specificity; D013844:Thiazoles
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; C539976:2-(6-(methylamino)pyridin-3-yl)-1,3-benzothiazol-6-ol; C582909:AZD2995; D000631:Aminopyridines; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D052160:Benzothiazoles; D001583:Benzoxazoles; D002250:Carbon Radioisotopes; D019275:Radiopharmaceuticals; D013844:Thiazoles