Department of Nuclear Medicine and PET Center, Aarhus University Hospital, Aarhus, Denmark.
Department of Nuclear Medicine and PET Center, Aarhus University Hospital, Aarhus, Denmark; Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
Nucl Med Biol. 2019 May-Jun;72-73:55-61. doi: 10.1016/j.nucmedbio.2019.07.006. Epub 2019 Jul 12.
[N-methyl-C]cholylsarcosine ([C]CSar) is a tracer for imaging and quantitative assessment of intrahepatic cholestatic liver diseases and drug-induced cholestasis by positron emission tomography (PET). The purpose of this study is to determine whole-body biodistribution and dosimetry of [C]CSar in healthy humans. The results are compared with findings in a patient with primary sclerosing cholangitis (PSC) and a patient with primary biliary cholangitis (PBC) as well as with preclinical findings in pigs. Radiosynthesis and quality control for preparation of [C]CSar for clinical use are also presented.
Radiosynthesis and quality control of [C]CSar were set up in compliance with Danish/European regulations. Both healthy participants (3 females, 3 males) and patients underwent whole-body PET/CT to determine the biodistribution of [C]CSar. The two patients were under treatment with ursodeoxycholic acid at the time of the study. Dosimetry was estimated from the PET data using the Olinda 2.0 software.
The radiosynthesis provided [C]CSar in a solution ready for injection. The biodistribution studies revealed that gallbladder wall, small intestine, and liver were critical organs in both healthy participants and patients with the gallbladder wall receiving the highest dose (up to 0.5 mGy/MBq). The gender-averaged (±SD) effective dose for the healthy participants was 6.2 ± 1.4 μSv/MBq. The effective dose for the PSC and the PBC patient was 5.2 and 7.0 μSv/MBq, respectively.
A radiosynthesis for preparation of [C]CSar for clinical use was developed and approved by the Danish Medicines Agency. The most critical organ was the gallbladder wall although the amount of [C]CSar in the gallbladder was found to vary significantly between individuals. The estimated effective dose for humans was comparable to that estimated in anesthetized pigs although the absorbed dose estimates to some organs, such as the stomach, was different. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: [C]CSar PET/CT enables detailed quantitative assessment of patients with cholestatic liver disease by tracing the separate hepatobiliary transport steps of endogenous bile acids. The present work offers a radiosynthetic method and dosimetry data suitable for clinical implementation of [C]CSar.
[N-甲基-C]胆酰基肌氨酸([C]CSar)是一种示踪剂，可通过正电子发射断层扫描(PET)对肝内胆汁淤积性肝病和药物诱导的胆汁淤积进行成像和定量评估。本研究旨在确定健康人体中[C]CSar 的全身生物分布和剂量。结果与原发性硬化性胆管炎(PSC)患者和原发性胆汁性胆管炎(PBC)患者的发现以及猪的临床前发现进行了比较。还介绍了用于临床使用的[C]CSar 的放射合成和质量控制。
根据丹麦/欧洲法规建立了[C]CSar 的放射合成和质量控制。健康参与者(3 名女性，3 名男性)和患者均进行全身 PET/CT 以确定[C]CSar 的生物分布。两名患者在研究期间接受熊去氧胆酸治疗。使用 Olinda 2.0 软件从 PET 数据估算剂量。
放射合成提供了可直接注射的[C]CSar 溶液。生物分布研究表明，胆囊壁、小肠和肝脏是健康参与者和胆囊壁接受最高剂量(高达 0.5 mGy/MBq)的患者的关键器官。健康参与者的平均(±SD)有效剂量为 6.2±1.4 μSv/MBq。PSC 和 PBC 患者的有效剂量分别为 5.2 和 7.0 μSv/MBq。
开发了一种用于临床使用的[C]CSar 的放射合成方法，并获得了丹麦药品管理局的批准。最关键的器官是胆囊壁，尽管个体之间胆囊内的[C]CSar 量差异很大。与在麻醉猪中估计的有效剂量相当，但对一些器官(如胃)的吸收剂量估计则不同。知识的进步及其对患者护理的影响：[C]CSar PET/CT 通过追踪内源性胆汁酸的单独肝胆转运步骤，能够对胆汁淤积性肝病患者进行详细的定量评估。本工作提供了一种适合临床应用[C]CSar 的放射合成方法和剂量学数据。
