1. Bio-Evaluation of 99mTc-Labeled Homodimeric Chalcone Derivative as Amyloid-β-Targeting Probe
- Author
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Garima Mann, Kanchan Chauhan, Vikas Kumar, Shivani Daksh, Nikhil Kumar, M. Thirumal, and Anupama Datta
- Subjects
beta-amyloid ,99mTc ,SPECT ,DTPA ,chalcone ,Medicine (General) ,R5-920 - Abstract
Chalcone derivatives have been successfully utilized for a range of biological applications and can cross the blood–brain barrier easily. β-amyloid-specific bis-chalcone derivative, 6,9-bis(carboxymethyl)-14-(4-[(E)-3-(4-(dimethylamino)phenyl)acryloyl]phenoxy)-3-(2-[(2-(4-[(E)-3-(4-(dimethylamino)phenyl)acryloyl]phenoxy)ethyl)amino]-2-oxoethyl)-11-oxo-3,6,9,12-tetraazatetradecanoic acid, DT(Ch)2, was analyzed using molecular modeling to explain the binding modes of the ligand with amyloid fibril and monomer followed by 99mTc-complexation in 95% yield and 98.7% efficiency. High-binding specificity of the radiocomplex was established following in vitro evaluation against 100-fold excess of DT(Ch)2. 99mTc–DT(Ch)2 exhibited 40% in the cingulate cortex followed by >25% in the hippocampus, a distribution pattern aligned to Alzheimer’s affected brain regions. Radiocomplex also displayed rapid plasma clearance followed by hepatobolic and renal modes of excretion.
- Published
- 2022
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