Human biodistribution, dosimetry, radiosynthesis and quality control of the bile acid PET tracer [N-methyl-11C]cholylsarcosine

introduction: [N-methyl-C-11]cholylsarcosine ([C-11]KSar) 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-11]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 predinical findings in pigs. Radiosynthesis and quality control for preparation of [C-11]CSar for clinical use are also presented. Methods: Radiosynthesis and quality control of [C-11]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-11]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. Results: The radiosynthesis provided [C-11]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 mu Sv/MBq. The effective dose for the PSC and the PBC patient was 52 and 7.0 mu Sv/MBq, respectively. Conclusion: A radiosynthesis for preparation of [C-11]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-11]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-11]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-11]CSar. (C) 2019 Elsevier Inc. All rights reserved.