title: Radiosynthesis and evaluation of [11C]BTA-1 and [11C]3'-Me-BTA-1 as potential radiotracers for in vivo imaging of beta-amyloid plaques.
abstract: OBJECTIVE
  To evaluate the in vitro and in vivo characteristics of [N-methyl-(11)C]2-(4'-(methylaminophenyl)-benzothiazole ([(11)C]BTA-1) as well as [N-methyl-(11)C]2-(3'-methyl-4'-(methylamino)phenyl)-benzothiazole ([(11)C]3'-Me-BTA-1) as diagnostic markers of amyloid-beta (Abeta) in Alzheimer's disease (AD).
  
  
  METHODS
  Brain uptake and clearance was determined in wild-type mice. Binding affinities (K(i)) of [(11)C]BTA-1 and [(11)C]3'-Me-BTA-1 for aggregated Abeta(1-40) fibrils were assessed. Autoradiography was performed on brain sections of AD patients. To demonstrate binding specificity in vivo BTA-1 was injected i.p. in transgenic mice (Tg2576). Brain sections were analysed consecutively. Additionally, a [(11)C]BTA-1 PET study of an AD patient and a healthy control was performed.
  
  
  RESULTS
  In mice brain uptake and clearance of [(11)C]BTA-1 is compatible with the half life of (11)C (2 min: 12.7 % ID/g; 30 min: 4.6% ID/g). In contrast clearance rate of [(11)C]3'-Me-BTA-1 is too slow (2 min 4% ID/g; 30 min 12% ID/g) to achieve sufficient clearance of free and non specifically bound radioactivity. K(i) of [(11)C]BTA-1 is 11 nmol/l and that of [(11)C]3'-Me-BTA-1 27 nmol/l. Both radioligands label Abeta selectively and specifically in AD patients and transgenic mice in vitro. The in vivo stained brain sections show a labelling of Abeta plaques. The AD patient has a higher prefrontal, parietal and striatal [(11)C]BTA-1 accumulation than the healthy control. Metabolite analysis revealed approximately 75% intact [(11)C]BTA-1 after 30min in plasma.[(11)C]BTA-1 is favourable for in vivo imaging of Abeta due to its rapid brain entry, sufficient clearance and good binding affinity for Abeta.
  
  
  CONCLUSIONS
  The ability to label Abeta plaques in vivo in human subjects supports the suitability of [(11)C]BTA-1 as a plaque imaging agent.
authors: Department of Nuclear Medicine, University Hospital Leuven, Herestraat 49, Leuven, Belgium.
authors: B
authors: B
authors: Neumaier
authors: S
authors: S
authors: Deisenhofer
authors: D
authors: D
authors: Fürst
authors: C A F
authors: CA
authors: von Arnim
authors: S
authors: S
authors: Thees
authors: A K
authors: AK
authors: Buck
authors: G
authors: G
authors: Glatting
authors: G B
authors: GB
authors: Landwehrmeyer
authors: B J
authors: BJ
authors: Krause
authors: H D
authors: HD
authors: Müller
authors: C
authors: C
authors: Sommer
authors: S N
authors: SN
authors: Reske
authors: F M
authors: FM
authors: Mottaghy
mesh_terms: D010129:4-Aminobenzoic Acid / Q000138:chemical synthesis / Q000493:pharmacokinetics; D000544:Alzheimer Disease / Q000000981:diagnostic imaging*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D052160:Benzothiazoles / Q000493:pharmacokinetics*; D001692:Biological Transport; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D062366:para-Aminobenzoates
chemical_list: D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D002250:Carbon Radioisotopes; C527159:N-methyl-(11)C)2-(4'-(methylaminophenyl)benzothiazole; D019275:Radiopharmaceuticals; D062366:para-Aminobenzoates; C015668:4-aminomethylbenzoic acid; D010129:4-Aminobenzoic Acid