Synthesis and biological evaluation of novel technetium-99m-labeled phenylquinoxaline derivatives as single photon emission computed tomography imaging probes targeting β-amyloid plaques in Alzheimer's disease

نویسندگان

  • Shimpei Iikuni
  • Masahiro Ono
  • Keiichi Tanimura
  • Hiroyuki Watanabe
  • Masashi Yoshimura
  • Hideo Saji
چکیده

The development of an imaging probe targeting b-amyloid (Ab) plaques in Alzheimer's disease labeled with technetium-99m, the most commonly used radioisotope for clinical diagnoses, has been strongly anticipated. In this study, we synthesized three novel Tc complexes with the phenylquinoxaline scaffold and evaluated their properties for imaging Ab plaques. The Tc and corresponding Re complexes were synthesized with bis(aminoethanethiol) (BAT) as a chelating ligand. In a binding affinity assay using recombinant Ab(1–42) aggregates in vitro, the Tc-labeled N,N-dimethylated phenylquinoxaline derivative (Tc-BAT-C3-PQ-1) and the corresponding Re complex showed sufficient affinity for Ab(1–42) aggregates. An in vivo biodistribution study in normal mice revealed that Tc-BAT-C3-PQ-1 showed a moderate initial brain uptake and a reasonable clearance from the brain. An ex vivo autoradiographic examination with Tc-BAT-C3-PQ-1 showed the marked labeling of Ab plaques in brain sections from Tg2576 transgenic mice but not age-matched controls. Tc-BAT-C3PQ-1 may be a potential single photon emission computed tomography probe for imaging Ab plaques in Alzheimer's disease.

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تاریخ انتشار 2017