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

  • Sci Rep. 2024 Jul 2;14(1):15100. doi: 10.1038/s41598-024-65668-z.
Sulan Xu  1  2 ,  Chun-Han Huang  1  2  3 ,  Christopher Eyermann  1  4 ,  Georgios V Georgakis  1  4 ,  Nashaat Turkman  5  6  7
Affiliations
  • 1. Stony Brook Cancer Center, Stony Brook, Long Island, NY, 11794, USA.
  • 2. Department of Radiology, School of Medicine, Stony Brook University, Stony Brook, NY, 11794, USA.
  • 3. Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY, 11794, USA.
  • 4. Department of Surgery, School of Medicine, Stony Brook University, Stony Brook, NY, 11794, USA.
  • 5. Stony Brook Cancer Center, Stony Brook, Long Island, NY, 11794, USA. [email protected].
  • 6. Department of Radiology, School of Medicine, Stony Brook University, Stony Brook, NY, 11794, USA. [email protected].
  • 7. Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY, 11794, USA. [email protected].
PMID: 38956204 DOI: 10.1038/s41598-024-65668-z
Abstract

The design and radiosynthesis of [18F]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 [18F]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 18F-radiolabel into a phenyl ring (18F-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.

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