A novel synthesis of 6''-[18 F]-fluoromaltotriose as a PET tracer for imaging bacterial infection.
A novel synthesis of 6''-[18 F]-fluoromaltotriose as a PET tracer for imaging bacterial infection.
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6-[18 F]-氟麦芽三糖的新合成作为细菌感染成像的 PET 示踪剂。
DOI：
10.1002/jlcr.3601
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发表时间：
2018
影响因子：
1.8
通讯作者：
Beinat,Corinne
中科院分区：
文献类型：
--
作者：
Namavari,Mohammad;Gowrishankar,Gayatri;Srinivasan,Ananth;Gambhir,SanjivS;Haywood,Thomas;Beinat,Corinne
本研究的目的是开发一种正电子发射断层扫描 (PET) 示踪剂，以可视化和监测对细菌感染的治疗反应。在我们不断努力寻找能够对细菌感染进行成像的基于麦芽糖的 PET 示踪剂的过程中，我们设计并制备了 6′′-[18F]氟麦芽三糖作为针对细菌麦芽糖糊精转运蛋白的第二代 PET 成像示踪剂。我们开发了合成 6′′-脱氧-6′′-[18F]氟-α-D-吡喃葡萄糖基-(1-4)-O-α-D-吡喃葡萄糖基-(1-4)-O-D-吡喃葡萄糖（6′′-[18F]-氟麦芽三糖）作为 细菌感染PET显像剂。 6′′-[18F]氟麦芽三糖由前体制备， 2′′,3′′,4′′-三-O-乙酰基-6′′-O-nosyl-α-D-吡喃葡萄糖基-(1-4)-O-2′,3′,6′-t ri-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 （全-O-乙酰基-6′′-O-nosyl-麦芽三糖4）。该方法利用前体 4 与无水 [18F]KF/Kryptofix 2.2.2 在二甲基甲酰胺 (DMF) 中于 85°C 反应 10 分钟，生成全-O-乙酰基-6''-脱氧-6-''[18F]-氟麦芽三糖 (7)。 7 中乙酰基保护基团的连续酸性和碱性水解产生 6''-[18F] 氟麦芽三糖 (8)。此外，通过二乙氨基三氟化硫反应和碱性水解，由全-O-乙酰基-6''-羟基麦芽三糖制备了冷的6''-[19F]氟麦芽三糖。 6′′-[18F]-氟麦芽三糖的成功合成已完成，放射化学产率为 8 ± 1.2%（衰减校正）。总合成时间为 120 分钟。 37°C 下 6''-[18F]-氟麦芽三糖的血清稳定性表明 6''-[18F]-氟麦芽三糖在 2 小时内保持完整。总之，我们通过直接氟化受保护的麦芽三糖的适当前体，成功合成了 6''-[18F]-氟麦芽三糖。
The aim of this study was to develop a positron emission tomography (PET) tracer to visualize and monitor therapeutic response to bacterial infections. In our continued efforts to find maltose based PET tracers that can image bacterial infections, we have designed and prepared 6′′‐[18F]fluoromaltotriose as a second generation PET imaging tracer targeting the maltodextrin transporter of bacteria. We have developed methods to synthesize 6′′‐deoxy‐6′′‐[18F]fluoro‐α‐D‐glucopyranosyl‐(1‐4)‐O‐α‐D‐glucopyranosyl‐(1‐4)‐O‐D‐glucopyranose (6′′‐[18F]‐fluoromaltotriose) as a bacterial infection PET imaging agent. 6′′‐[18F]fluoromaltotriose was prepared from precursor, 2′′,3′′,4′′‐tri‐O‐acetyl‐6′′‐O‐nosyl‐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 (per‐O‐acetyl‐6′′‐O‐nosyl‐maltotriose4). This method utilizes the reaction between precursor4and anhydrous [18F]KF/Kryptofix 2.2.2 in dimethylformamide (DMF) at 85°C for 10 minutes to yield per‐O‐acetyl‐6′′‐deoxy‐6‐′′ [18F]‐fluoromaltotriose (7). Successive acidic and basic hydrolysis of the acetyl protecting groups in7produced 6′′‐[18F]fluoromaltotriose (8). Also, cold 6′′‐ [19F]fluoromaltotriose was prepared from per‐O‐acetyl‐6′′‐hydroxymaltotriose via a diethylaminosulfur trifluoride reaction followed by a basic hydrolysis. A successful synthesis of 6′′‐[18F]‐fluoromaltotriose has been accomplished in 8 ± 1.2% radiochemical yield (decay corrected). Total synthesis time was 120 minutes. Serum stability of 6′′‐[18F]fluoromaltotriose at 37°C indicated that 6′′‐[18F]‐fluoromaltotriose remained intact up to 2 hours. In conclusion, we have successfully synthesized 6′′‐[18F]‐fluoromaltotriose via direct fluorination of an appropriate precursor of a protected maltotriose.