Acetylated Benzothiazolone as Homobivalent SPECT Metallo-Radiopharmaceutical ^99mTc-(6-AcBTZ)₂DTPA: Design, Synthesis, and Preclinical Evaluation for Mapping 5-HT_1A/7 Receptors.

ABSTRACT: Mapping different structural forms of serotonin subtypes 5-HT_1A-5-HT₇ using a selective-specific ligand with good pharmacokinetics and brain permeability can open avenues for personalized medication in depressed population. Herein, the selective 5-HT_1A/7 antagonist, modified for enhanced brain permeation, is developed as a homobivalent ligand, (6-AcBTZ)₂DTPA. After in-depth computational studies to probe the binding mechanism, two-step synthesis lead to (6-AcBTZ)₂DTPA. Biocompatibility studies indicated cytocompatibility with 3.6-1.64% cell death (0.1 mM-1 pM) and hemocompatibility with 2.33% hemolysis of human erythrocytes. When ^99mTc-radiolabeled in a quantitative yield (98%), a stable preparation was obtained with 7.4 and

SUBMITTER: Jha P 

PROVIDER: S-EPMC6647941 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature