New synthesis of 6″‐[¹⁸F]fluoromaltotriose for positron emission tomography imaging of bacterial infection

Abstract

6″‐[18F]fluoromaltotriose is a positron emission tomography tracer that can differentiate between bacterial infection and inflammation in vivo. Bacteria‐specific uptake of 6″‐[18F]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″‐[18F]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″‐[18F]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″‐[18F]fluoromaltotriose would be critical in advancing this positron emission tomography tracer into clinical trials for imaging bacterial infections.

Recently developed radiopharmaceuticals for bacterial infection imaging

“…[ 18 F]fluoromaltotriose Gabr et al (2020) developed a shortened, more reliable radiosynthesis method for [ 18 F] fluoromaltotriose, based on their previous work, with the unambiguous assignment of the 18 F-position (see Fig. 15).…”

Pathophysiology and Molecular Imaging of Diabetic Foot Infections

“…PET imaging performed with 18 F-maltohexose demonstrated uptake in both gram positive and gram negative bacteria [143], although poor signal-to-noise ratios limit this tracer's clinical application. The second generation tracer 6 -18 F-fluoromaltotriose has improved signal-to-noise ratios while maintaining bacterial-selective uptake in vitro and in vivo [144,145].…”

Synthesis and Evaluation of Fluorine-18-Labeled L-Rhamnose Derivatives

“…More recently, other radiolabeled sugars have been developed for different purposes, such as imaging tumors [8] but more commonly for imaging different infections [9][10][11]. L-Rhamnose is a naturally occurring 6-deoxy sugar that is commercially used in the food, beverage, cosmetic and pharmaceutical industries (Figure 1, compound 1) [12,13], but has no role in mammalian metabolism [14].…”