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

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.

• Authors: Hiroyuki Watanabe, Masahiro Ono, Hiroyuki Kimura, Shinya Kagawa, Ryuichi Nishii, Takeshi Fuchigami, Mamoru Haratake, Morio Nakayama, Hideo Saji
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 21 Issue 21 Pg. 6519-22 (Nov 01 2011) ISSN: 1464-3405 [Electronic] England
• PMID: 21920750 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• Amyloid beta-Peptides
• Fluorine Radioisotopes
• Iodine Radioisotopes

Topics

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