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使用 Trasis AllInOne 模块,基于全自动盒式合成 2-脱氧-2-[F]氟代纤维二糖。

Fully Automated Cassette-Based Synthesis of 2-Deoxy-2-[F]Fluorocellobiose Using Trasis AllInOne Module.

机构信息

Chemistry and Synthesis Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Rockville, Maryland, USA.

Center for Infectious Disease Imaging, Radiology and Imaging Sciences, Clinical Center (CC), National Institutes of Health (NIH), Bethesda, Maryland, USA.

出版信息

J Labelled Comp Radiopharm. 2024 Jul;67(9):308-313. doi: 10.1002/jlcr.4116. Epub 2024 Jul 9.

DOI:10.1002/jlcr.4116
PMID:38982015
Abstract

Due to the continuous rise in global incidence and severity of invasive fungal infections (IFIs), particularly among immunocompromised and immunodeficient patients, there is an urgent demand for swift and accurate fungal pathogen diagnosis. Therefore, the need for fungal-specific positron emission tomography (PET) imaging agents that can detect the infection in the early stages is increasing. Cellobiose, a disaccharide, is readily metabolized by fungal pathogens such as Aspergillus species. Recently, our group reported fluorine-18 labeled cellobiose, 2-deoxy-2-[F]fluorocellobiose ([F]FCB), for specific imaging of Aspergillus infection. The positive imaging findings with very low background signal on delayed imaging make this ligand a promising fungal-specific imaging ligand. Inspired by this result, the decision was made to automate the radiolabeling procedure for better reproducibility and to facilitate clinical translation. A Trasis AllInOne (Trasis AIO) automated module was used for this purpose. The reagent vials contain commercially available 2-deoxy-2-[F]fluoroglucose ([F]FDG), glucose-1-phosphate, and enzyme (cellobiose phosphorylase). A Sep-Pak cartridge was used to purify the tracer. The overall radiochemical yield was 50%-70% (n = 6, decay corrected) in 75-min synthesis time with a radiochemical purity of > 98%. This is a highly reliable protocol to produce current good manufacturing practice (cGMP)-compliant [F]FCB for clinical PET imaging.

摘要

由于全球侵袭性真菌感染 (IFI) 的发病率和严重程度持续上升,特别是在免疫功能低下和免疫缺陷患者中,因此迫切需要快速准确的真菌病原体诊断。因此,对能够在早期检测感染的真菌特异性正电子发射断层扫描 (PET) 成像剂的需求不断增加。纤维二糖是一种二糖,很容易被曲霉属等真菌病原体代谢。最近,我们小组报道了氟-18 标记的纤维二糖,2-脱氧-2-[F]氟代纤维二糖 ([F]FCB),可特异性成像曲霉属感染。延迟成像时,背景信号非常低,阳性成像结果表明该配体是一种很有前途的真菌特异性成像配体。受此结果启发,我们决定自动化标记程序以提高重现性并促进临床转化。为此目的使用了 Trasis AllInOne (Trasis AIO) 自动化模块。试剂小瓶中含有市售的 2-脱氧-2-[F]氟代葡萄糖 ([F]FDG)、葡萄糖-1-磷酸和酶 (纤维二糖磷酸化酶)。使用 Sep-Pak 小柱对示踪剂进行纯化。在 75 分钟的合成时间内,总放射化学产率为 50%-70%(n=6,衰变校正),放射化学纯度>98%。这是一种非常可靠的方案,可以生产符合现行良好生产规范 (cGMP) 的 [F]FCB 用于临床 PET 成像。

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