Aromatic radiofluorination and biological evaluation of 2-aryl-6-[18F]fluorobenzothiazoles as a potential positron emission tomography imaging probe for β-amyloid plaques

Bioorg Med Chem. 2011 May 1;19(9):2980-90. doi: 10.1016/j.bmc.2011.03.029. Epub 2011 Mar 21.

Abstract

To develop agents for radionuclide imaging Aβ plaques in vivo, we prepared three fluorine-substituted analogs of arylbenzothiazole class; compound 2 has a high affinity for Aβ (K(i)=5.5nM) and the specific binding to Aβ in fluorescent staining. In preparation for the synthesis of these arylbenzothiazole analogs in radiolabeled form as an Aβ plaques-specific positron emission tomography (PET) imaging probe, we investigated synthetic route suitable for its labeling with the short-lived PET radionuclide fluorine-18 (t(1/2)=110min) and diaryliodonium tosylate precursors (12, 13a-e and 14). 2-Aryl-6-[(18)F]fluorobenzothiazoles ([(18)F]1-3) were synthesized in efficiently short reaction times (40-60min) with high radiochemical yields (19-40%), purities (>95%) and specific activities (85-118GBq/μmol). Tissue distribution studies showed that high radioactivity of [(18)F]2 accumulated in the brain with rapid clearance in healthy mice. Radioactive metabolites were analyzed in brain samples of mice and corresponded to 81% of parent remained by 30min after a tail-vein injection. These results suggest that [(18)F]2 is a promising probe for evaluation of Aβ plaques imaging in brain using PET.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzothiazoles / chemical synthesis
  • Benzothiazoles / chemistry*
  • Brain / metabolism
  • Brain / pathology
  • Fluorescent Dyes / chemical synthesis
  • Fluorescent Dyes / chemistry
  • Fluorine Radioisotopes / chemistry
  • Kinetics
  • Mice
  • Mice, Transgenic
  • Plaque, Amyloid / chemistry
  • Plaque, Amyloid / metabolism*
  • Positron-Emission Tomography
  • Radiopharmaceuticals / chemistry*
  • Tissue Distribution

Substances

  • 2-(4'-methylaminophenyl)-6-fluorobenzothiazole
  • Benzothiazoles
  • Fluorescent Dyes
  • Fluorine Radioisotopes
  • Radiopharmaceuticals