New synthesis of 6″-[ F]fluoromaltotriose for positron emission tomography imaging of bacterial infection.

6″-[ F]fluoromaltotriose is a positron emission tomography tracer that can differentiate between bacterial infection and inflammation in vivo. Bacteria-specific uptake of 6″-[ F]fluoromaltotriose is attributed to the targeting of maltodextrin transporter in bacteria that is absent in mammalian cells. Herein, we report a new synthesis of 6″-[ F]fluoromaltotriose as a key step for its clinical translation. In comparison with the previously reported synthesis, the new synthesis features unambiguous assignment of the fluorine-18 position on the maltotriose unit. The new method utilizes direct fluorination of 2″,3″,4″-tri-O-acetyl-6″-O-trifyl-α-D-glucopyranosyl-(1-4)-O-2',3',6'-tri-O-acetyl-α-D-glucopyranosyl-(1-4)-1,2,3,6-tetra-O-acetyl-D-glucopyranose followed by basic hydrolysis. Radiolabeling of the new maltotriose triflate precursor proceeds using a single HPLC purification step, which results in shorter reaction time in comparison with the previously reported synthesis. Successful synthesis of 6″-[ F]fluoromaltotriose has been achieved in 3.5 ± 0.3% radiochemical yield (decay corrected, n = 7) and radiochemical purity above 95%. The efficient radiosynthesis of 6″-[ F]fluoromaltotriose would be critical in advancing this positron emission tomography tracer into clinical trials for imaging bacterial infections.