Synthesis and evaluation of 18F-fluoroethylated benzothiazole derivatives for in vivo imaging of amyloid plaques in Alzheimer's disease.

Abstract

Amyloid aggregates play a major role in the development of Alzheimer's disease. Targeting these aggregates by PET probes enables non-invasively the detection and quantification of amyloid deposit distribution in human brains. Based on benzothiazole core structure a series of amyloid imaging agents were developed. Currently [(11)C]2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole (Pittsburgh Compound-B (PIB) is the most specific and widely used amyloid imaging ligand. But due to the short half life of (11)C, longer lived (18)F-labeled derivatives offer logistic advantages and higher contrast images. In this work, three different [(18)F]fluoroethoxy-substituted benzothiazole derivatives ([(18)F]2-(4'-(methylamino)phenyl)-6-(2-fluoroethoxy)benzothiazole, [(18)F]2-((2'-(2-fluoroethoxy)-4'-amino)phenyl)benzothiazole and [(18)F]2-(3'-((2-fluoroethoxy)-4'-amino)phenyl)benzothiazole) were synthesized via [(18)F]fluoroethylation. The latter two derivatives with fluoroethoxy-substitution on the aromatic amino group showed very low binding affinity for amyloid aggregates. In contrast [(18)F]2-(4'-(methylamino)phenyl)-6-(2-fluoroethoxy)benzothiazole with [(18)F]fluoroethoxy-substitution in 6-position showed excellent amyloid imaging properties with respect to lipophilicity, brain entry and brain clearance in normal SCID mice, amyloid plaque binding affinity and specificity.

• Authors: B Neumaier, S Deisenhofer, C Sommer, C Solbach, S N Reske, F Mottaghy
• Journal: Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine (Appl Radiat Isot) Vol. 68 Issue 6 Pg. 1066-72 (Jun 2010) ISSN: 1872-9800 [Electronic] England
• PMID: 20089413 (Publication Type: Journal Article)
• Copyright: Copyright 2010 Elsevier Ltd. All rights reserved.

Chemical References

• 2-(4'-(methylamino)phenyl)-6-(2-fluoroethoxy)benzothiazole
• Amyloid
• Benzothiazoles
• Fluorine Radioisotopes
• Radiopharmaceuticals

Topics

• Alzheimer Disease (diagnostic imaging)
• Amyloid (metabolism)
• Animals
• Benzothiazoles (chemical synthesis, pharmacokinetics)
• Brain (metabolism)
• Fluorine Radioisotopes
• Mice
• Mice, SCID
• Plaque, Amyloid (metabolism)
• Positron-Emission Tomography (methods)
• Radiopharmaceuticals (chemical synthesis, pharmacokinetics)