Bio-X Program and Molecular Imaging Program at Stanford (MIPS), Stanford University, Stanford, California, USA.
Department of Radiology, Stanford University, Stanford, California, USA.
J Labelled Comp Radiopharm. 2020 Sep;63(11):466-475. doi: 10.1002/jlcr.3868. Epub 2020 Jul 21.
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.
6″-[F]氟麦芽三糖是一种正电子发射断层扫描示踪剂，可在体内区分细菌感染和炎症。细菌对 6″-[F]氟麦芽三糖的特异性摄取归因于细菌中麦芽糖转运蛋白的靶向，而哺乳动物细胞中不存在该蛋白。在此，我们报告了 6″-[F]氟麦芽三糖的新合成方法，这是其临床转化的关键步骤。与之前报道的合成方法相比，新的合成方法明确指定了麦芽三糖单元上的氟-18 位置。该新方法利用 2″、3″、4″-三-O-乙酰基-6″-O-三氟甲磺酸基-α-D-吡喃葡萄糖基-(1-4)-O-2'、3'、6'-三-O-乙酰基-α-D-吡喃葡萄糖基-(1-4)-1、2、3、6-四-O-乙酰基-D-吡喃葡萄糖的直接氟化，然后进行碱性水解。新的麦芽三糖三氟甲磺酸酯前体的放射性标记仅需通过单一 HPLC 纯化步骤即可完成，与之前报道的合成方法相比，反应时间更短。已成功以 3.5±0.3%（衰变校正，n=7）的放射性化学产率（n=7）和高于 95%的放射化学纯度实现了 6″-[F]氟麦芽三糖的合成。6″-[F]氟麦芽三糖的高效放射性合成对于将这种正电子发射断层扫描示踪剂推进到用于成像细菌感染的临床试验中至关重要。
