Chemoenzymatic Syntheses of Fluorine-18-Labeled Disaccharides from [18F] FDG Yield Potent Sensors of Living Bacteria In Vivo

• DOI: 10.1021/jacs.3c03338
• Publication Date: 2023-08-03T20:49:36Z
• Authors: Alexandre M. Sorlin; Marina López-Álvarez; Sarah J. Rabbitt; Aryn A. Alanizi; Rebecca Shuere; Kondapa Naidu Bobba; Joseph Blecha; Sasank Sakhamuri; Michael J. Evans; Kenneth W. Bayles; Robert R. Flavell; Oren S. Rosenberg; Renuka Sriram; Tom Desmet; Bernd Nidetzky; Joanne Engel; Michael A. Ohliger; James S. Fraser; David M. Wilson
• Keywords: Acinetobacter baumannii; Radiosynthesis

Chemoenzymatic techniques have been applied extensively to pharmaceutical development, most effectively when routine synthetic methods fail. The regioselective and stereoselective construction of structurally complex glycans is an elegant application this approach that seldom positron emission tomography (PET) tracers. We sought a method dimerize 2-deoxy-[18F]-fluoro-d-glucose ([18F]FDG), the common tracer used in clinical imaging, form [18F]-labeled disaccharides for detecting microorganisms vivo based on their bacteria-specific glycan incorporation. When [18F]FDG was reacted with β-d-glucose-1-phosphate presence maltose phosphorylase, α-1,4- α-1,3-linked products 2-deoxy-[18F]-fluoro-maltose ([18F]FDM) 2-deoxy-2-[18F]-fluoro-sakebiose ([18F]FSK) were obtained. This further extended use trehalose (α,α-1,1), laminaribiose (β-1,3), cellobiose (β-1,4) phosphorylases synthesize 2-deoxy-2-[18F]fluoro-trehalose ([18F]FDT), 2-deoxy-2-[18F]fluoro-laminaribiose ([18F]FDL), 2-deoxy-2-[18F]fluoro-cellobiose ([18F]FDC). subsequently tested [18F]FDM [18F]FSK vitro, showing accumulation by several clinically relevant pathogens including Staphylococcus aureus Acinetobacter baumannii, demonstrated specific uptake vivo. Both stable human serum high preclinical infection models. ease sensitivity S. methicillin-resistant (MRSA) strains strongly justify translation these tracers infected patients. Furthermore, work suggests chemoenzymatic radiosyntheses [18F]FDG-derived oligomers will afford wide array PET radiotracers infectious oncologic applications.