Radiosynthesis and evaluation of [11C]BTA-1 and [11C]3'-Me-BTA-1 as potential radiotracers for in vivo imaging of beta-amyloid plaques

Nuklearmedizin. 2007;46(6):271-80.


Aim: 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).

Material, 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.

Conclusion: The ability to label Abeta plaques in vivo in human subjects supports the suitability of [(11)C]BTA-1 as a plaque imaging agent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Aminobenzoic Acid / chemical synthesis
  • 4-Aminobenzoic Acid / pharmacokinetics
  • Alzheimer Disease / diagnostic imaging*
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Benzothiazoles / pharmacokinetics*
  • Biological Transport
  • Brain / diagnostic imaging*
  • Brain / metabolism
  • Brain / pathology
  • Carbon Radioisotopes / pharmacokinetics
  • Humans
  • Mice
  • Mice, Transgenic
  • Positron-Emission Tomography
  • Radiopharmaceuticals / pharmacokinetics
  • para-Aminobenzoates*


  • Amyloid beta-Peptides
  • Benzothiazoles
  • Carbon Radioisotopes
  • N-methyl-(11)C)2-(4'-(methylaminophenyl)benzothiazole
  • Radiopharmaceuticals
  • para-Aminobenzoates
  • 4-aminomethylbenzoic acid
  • 4-Aminobenzoic Acid