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Title: Evaluation of 64Cu-Based Radiopharmaceuticals that Target Aβ Peptide Aggregates as Diagnostic Tools for Alzheimer’s Disease

Positron emission tomography (PET) imaging agents that detect amyloid plaques containing amyloid beta (Aβ) peptide aggregates in the brain of Alzheimer’s disease (AD) patients have been successfully developed and recently approved by the FDA for clinical use. However, the short half-lives of the currently used radionuclides 11C (20.4 min) and 18F (109.8 min) may limit the widespread use of these imaging agents. Therefore, we have begun to evaluate novel AD diagnostic agents that can be radiolabeled with 64Cu, a radionuclide with a half-life of 12.7 h, ideal for PET imaging. Described here in this paper are a series of bifunctional chelators (BFCs), L 1–L 5, that were designed to tightly bind 64Cu and shown to interact with Aβ aggregates both in vitro and in transgenic AD mouse brain sections. Importantly, biodistribution studies show that these compounds exhibit promising brain uptake and rapid clearance in wild-type mice, and initial microPET imaging studies of transgenic AD mice suggest that these compounds could serve as lead compounds for the development of improved diagnostic agents for AD.
Authors:
 [1] ;  [2] ;  [3] ;  [2] ;  [4] ;  [1] ; ORCiD logo [5]
  1. Washington Univ. School of Medicine, St. Louis, MO (United States). Mallinckrodt Inst. of Radiology; Washington Univ. School of Medicine, St. Louis, MO (United States). Dept. of Radiation Oncology
  2. Washington Univ., St. Louis, MO (United States). Dept. of Chemistry
  3. Washington Univ. School of Medicine, St. Louis, MO (United States). Dept. of Radiation Oncology
  4. A.T. Still Univ. of Health Sciences, Kirksville, MO (United States). Kirksville College of Osteopathic Medicine, Dept. of Pharmacology
  5. Washington Univ., St. Louis, MO (United States). Dept. of Chemistry; Washington Univ. School of Medicine, St. Louis, MO (United States). Hope Center for Neurological Disorders
Publication Date:
Grant/Contract Number:
SC0002032
Type:
Accepted Manuscript
Journal Name:
Journal of the American Chemical Society
Additional Journal Information:
Journal Volume: 139; Journal Issue: 36; Journal ID: ISSN 0002-7863
Publisher:
American Chemical Society (ACS)
Research Org:
Washington Univ., St. Louis, MO (United States). School of Medicine
Sponsoring Org:
USDOE; National Institutes of Health (NIH)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE
OSTI Identifier:
1474065