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

Bandara, Nilantha; Sharma, Anuj K.; Krieger, Stephanie; Schultz, Jason W.; Han, Byung Hee; Rogers, Buck E.; Mirica, Liviu M.

doi:10.1021/jacs.7b05937

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

Journal Article · Mon Aug 21 00:00:00 EDT 2017 · Journal of the American Chemical Society

DOI:https://doi.org/10.1021/jacs.7b05937· OSTI ID:1474065

Bandara, Nilantha ^[1]; Sharma, Anuj K. ^[2]; Krieger, Stephanie ^[3]; Schultz, Jason W. ^[2]; Han, Byung Hee ^[4]; Rogers, Buck E. ^[1];

^[5]

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
Washington Univ., St. Louis, MO (United States). Dept. of Chemistry
Washington Univ. School of Medicine, St. Louis, MO (United States). Dept. of Radiation Oncology
A.T. Still Univ. of Health Sciences, Kirksville, MO (United States). Kirksville College of Osteopathic Medicine, Dept. of Pharmacology
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

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), L₁–L₅, 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.

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Research Organization:: Washington Univ., St. Louis, MO (United States). School of Medicine

Sponsoring Organization:: USDOE; National Institutes of Health (NIH)

Grant/Contract Number:: SC0002032

OSTI ID:: 1474065

Journal Information:: Journal of the American Chemical Society, Vol. 139, Issue 36; ISSN 0002-7863

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 38 works

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