Design and radiosynthesis of class-IIa HDAC inhibitor with high molar activity via repositioning the 18F-radiolabel

• Published in: Scientific reports Vol. 14; no. 1; pp. 15100 - 8
• Main Authors: Xu, Sulan, Huang, Chun-Han, Eyermann, Christopher, Georgakis, Georgios V, Turkman, Nashaat
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 02.07.2024; Nature Publishing Group UK; Nature Portfolio
• Subjects: Acids; Chemical synthesis; Design; Fluorides; Histone deacetylase; Histones
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-65668-z

Abstract The design and radiosynthesis of [ 18 F]NT376, a high potency inhibitor of class-IIa histone deacetylases (HDAC) is reported. We utilized a three-step radiochemical approach that led to the radiosynthesis of [ 18 F]NT376 in a good radiochemical yield, (17.0 ± 3%, decay corrected), high radiochemical purity (> 97%) and relatively high molar activity of 185.0 GBq/µmol (> 5.0 Ci/µmol). The repositioning of the 18 F-radiolabel into a phenyl ring ( 18 F-Fluoro-aryl) of the class-IIa HDAC inhibitor avoided the shortcomings of the direct radiolabeling of the 5-trifluoromethyl-1,2,4-oxadiazole moiety that was reported by us previously and was associated with low molar activity (0.74–1.51 GBq/µmol, 20–41 mCi/µmol). This radiochemical approach could find a wider application for radiolabeling similar molecules with good radiochemical yield and high molar activity.