(68)Ga-Bivalent Polypegylated Styrylpyridine Conjugates for Imaging Aβ Plaques in Cerebral Amyloid Angiopathy

Bioconjug Chem. 2016 May 18;27(5):1314-23. doi: 10.1021/acs.bioconjchem.6b00127. Epub 2016 Apr 20.

Abstract

Aβ plaques deposited on blood vessels are associated with cerebral amyloid angiopathy (CAA). In an effort to selectively map these Aβ plaques, we are reporting a new series of (68)Ga labeled styrylpyridine derivatives with high molecular weights. In vitro binding to Aβ plaques in post-mortem Alzheimer's disease (AD) brain tissue showed that these (68)Ga labeled bivalent styrylpyridines displayed good affinities and specificity (Ki < 30 nM). In vitro autoradiography using post-mortem AD brain sections showed specific binding of these (68)Ga complexes to Aβ plaques. Biodistribution studies in normal mice showed very low initial brain uptakes (<0.3% dose/g) indicating a low blood-brain barrier (BBB) penetration. The preliminary results suggest that (68)Ga labeled bivalent styrylpyridines may be promising candidates as PET imaging radiotracers for detecting CAA.

MeSH terms

  • Animals
  • Blood-Brain Barrier / metabolism
  • Cerebral Amyloid Angiopathy / complications*
  • Gallium Radioisotopes*
  • Mice
  • Plaque, Amyloid / complications*
  • Plaque, Amyloid / diagnostic imaging*
  • Polyethylene Glycols / chemistry*
  • Positron-Emission Tomography / methods*
  • Pyridines / chemistry*
  • Pyridines / metabolism
  • Pyridines / pharmacokinetics
  • Styrenes / chemistry*
  • Styrenes / metabolism
  • Styrenes / pharmacokinetics
  • Tissue Distribution

Substances

  • Gallium Radioisotopes
  • Pyridines
  • Styrenes
  • 4-stilbazole
  • Polyethylene Glycols