A dual fluorinated and iodinated radiotracer for PET and SPECT imaging of β-amyloid plaques in the brain

Bioorg Med Chem Lett. 2011 Nov 1;21(21):6519-22. doi: 10.1016/j.bmcl.2011.08.063. Epub 2011 Aug 24.

Abstract

We report a fluorinated and iodinated radiotracer as a probe for PET/SPECT to detect of β-amyloid (Aβ) plaques in the brain of patients with Alzheimer's disease (AD). We successfully designed and synthesized the fluorinated and iodinated aurone derivative (3) and its radiolabels ([(125)I]3 and [(18)F]3). In binding experiments in vitro, 3 showed high affinity for Aβ aggregates (K(i)=6.81nM). In brain sections of AD model mice, 3 intensely stained Aβ plaques. Furthermore, a specific plaque labeling signal was observed on the autoradiography of postmortem AD brain sections using [(125)I]3. In biodistribution experiments using normal mice, [(125)I]3 and [(18)F]3 displayed good uptake into and a rapid washout from the brain, properties highly desirable for Aβ imaging agents. These results suggest that 3 may function as a PET/SPECT dual imaging agent for detecting Aβ plaques in AD brains.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / metabolism
  • Amyloid beta-Peptides / metabolism*
  • Autoradiography
  • Brain / diagnostic imaging*
  • Brain / metabolism
  • Fluorine Radioisotopes* / pharmacokinetics
  • Humans
  • Iodine Radioisotopes* / pharmacokinetics
  • Positron-Emission Tomography / methods*
  • Tissue Distribution
  • Tomography, Emission-Computed, Single-Photon / methods*

Substances

  • Amyloid beta-Peptides
  • Fluorine Radioisotopes
  • Iodine Radioisotopes