2-(4-Hydroxyphenyl)benzothiazole dicarboxylate ester TACN chelators for 64Cu PET imaging in Alzheimer's disease

Dalton Trans. 2022 Jan 17;51(3):1216-1224. doi: 10.1039/d1dt02767k.

Abstract

Herein we report a new series of bifunctional chelators (BFCs) with high affinity for amyloid β aggregates, strong binding affinity towards Cu(II), and favorable lipophilicity for potential blood-brain barrier (BBB) penetration. The alkyl carboxylate ester pendant arms show high binding affinity towards Cu(II). The BFCs form stable 64Cu-radiolabeled complexes and exhibit favorable partition coefficient (log D) values of 0.75-0.95. Among the five compounds tested, 64Cu-YW-1 and 64Cu-YW-13 complexes exhibit significant staining of amyloid plaques in ex vivo autoradiography studies.

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Amyloidogenic Proteins / genetics
  • Amyloidogenic Proteins / metabolism*
  • Animals
  • Benzothiazoles
  • Chelating Agents / chemistry*
  • Copper Radioisotopes*
  • Mice
  • Mice, Transgenic
  • Molecular Structure
  • Mutation
  • Positron-Emission Tomography*
  • Radiopharmaceuticals / chemical synthesis
  • Radiopharmaceuticals / pharmacology

Substances

  • Amyloidogenic Proteins
  • Benzothiazoles
  • Chelating Agents
  • Copper Radioisotopes
  • Copper-64
  • Radiopharmaceuticals