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Design and synthesis of astatinated benzothiazole compounds for their potential use in Targeted Alpha Therapy (TAT) strategies to treat Alzheimer's disease-associated amyloid plaques

Journal Article · · Applied Radiation and Isotopes
 [1];  [2];  [1];  [2];  [2];  [1];  [1]
  1. Univ. of Utah, Salt Lake City, UT (United States)
  2. Univ. of Washington, Seattle, WA (United States)
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Alzheimer's disease (AD) is a terminal neurodegenerative disease characterized by the buildup of amyloid fibrils, amorphous aggregates and tauopathies. Several treatment modalities, which rely on various biological processes to reduce disease burden, have been largely ineffective at treating Alzheimer's disease. Targeted alpha therapy (TAT) has demonstrated positive results in the treatment of cancer. Benzothiazole derivatives have been successfully shown to target these plaques and are used in several imaging applications. One such derivative, Flutemetamol (VizamylTM) is an FDA approved diagnostic tool for PET imaging of AD-associated plaques. We report the radiolabeling of benzothiazole derivatives with 211At, a 7.2 h alpha emitting radionuclide, using a copper catalyzed reaction with a boronic acid precursor molecule. In conclusion, our final compound [211At]3'-At-PIB-OMe had a radiochemical yield of 55% and was found to be stable for at least 3 h in phosphate buffered saline.
Research Organization:
USDOE Office of Science (SC), Office of Isotope R&D and Production (IRP)
Sponsoring Organization:
National Institutes of Health (NIH); USDOE
OSTI ID:
2424946
Journal Information:
Applied Radiation and Isotopes, Journal Name: Applied Radiation and Isotopes Journal Issue: C Vol. 191; ISSN 0969-8043
Publisher:
ElsevierCopyright Statement
Country of Publication:
United States
Language:
English

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Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
Alzheimer's disease
Amyloid
Astatine-211
Chemistry
Copper catalyzed astatination
Nuclear Science & Technology
Radiochemistry
Radiology
Nuclear Medicine & Medical Imaging
Targeted alpha therapy