PET/CT Scans Using the Tracer 11C-Csar, a Bile Acid Analog, to Depict and Visualize Cholestatic Disorders in Patients with Genetic Liver Disorders and Healthy Individuals

Condition(s) studied

Study summary

Purpose The primary goal is to study liver diseases with defects in bile excretion. Investigators aim to do this using a radioactive tracer that mimics human bile and can be visualized with a PET/CT scanner. This will help us understand where these defects occur and how they might be treated in the future.

Background Patients with liver diseases affecting bile excretion are at risk of developing cirrhosis. When bile cannot be excreted normally, it accumulates in the liver, damaging its function. It can also build up in the skin, causing yellowing and itching. Currently, patients are monitored using blood tests that do not always reflect the severity of liver disease. There are a few medications available, but they have limited efficacy.

Advanced PET/CT scanning with the radioactive tracer 11C-Csar offers a way to investigate this. 11C-Csar has been developed, tested, and approved for human use at Aarhus University Hospital and has been used in previous patient studies.

The study aims to use this method to show how 11C-Csar moves through the liver and bile ducts in both healthy individuals and patients with a genetic liver disease. Investigators aim to:

* Observe how defects affect the liver handling of bile acids.
* Determine the excretion kinetics of 11C-Csar, including specific rate constants.
* Compare standard blood tests with 11C-Csar PET/CT findings to assess how well blood tests reflect actual liver damage.
* Visualize potential targets for future interventions.

Study Plan The scientific study involves a single examination day at the Department of Nuclear Medicine and PET. Participants will arrive fasting in the morning. An intravenous line will be placed in both arm veins, a catheter in a wrist vessel, and a hepatic vein catheter. The hepatic vein catheter will be inserted by a trained liver specialist using local anesthesia and ultrasound guidance, confirmed by X-ray. The tracer 11C-Csar and the dye indocyanine green (ICG) will be administered through the IV lines. ICG will be infused 90 minutes before scanning, and 11C-Csar will be administered at the start of the scan. Blood samples will be taken from the liver and wrist during the scan, which lasts about 45 minutes. After the scan, the catheters will be removed, and the participant can go home shortly after. Approximately 250-300 ml of blood will be drawn, which poses no risk to the participants. The total participation time is expected to be around 4 hours. Some patients may be offered a second scan if they develop new symptoms, repeating the scan when liver blood tests normalize.

Participants Patients with bile accumulation liver diseases will be informed of the study during visits to the Department of Hepatology and Gastroenterology, AUH. Healthy controls will be recruited through advertisements on webpages dedicated for the purpuse. Interested individuals will receive written information.

Side Effects, Risks, and Discomfort The risk of phlebitis and bleeding from IV insertion is minimal, as these procedures are performed daily.

The total radiation exposure from the PET/CT scan with 11C-Csar is 2.5 mSv.

Funding The study is researcher-initiated, with no financial interests for the involved researchers.

Publication of Results Both negative, positive, and inconclusive results will be published. The study results will be submitted to peer-reviewed international journals in liver disease and/or radiology and presented at national and international scientific conferences.

Ethics The study will be conducted following the principles of the Helsinki Declaration II with amendments and after approval by the Regional Ethics Committee for Midtjylland. While there is no immediate benefit for patients, the results will enhance our understanding of liver disease with bile acid accumulation. Investigators believe the risks and potential side effects are outweighed by the expected benefits.

Eligibility

Primary outcome measure(s)

• The aim of this study is to apply the 11C-CSAR PET/CT method to quantify hepatobiliary secretion kinetics of 11C-Csar in both healthy human participants and patients with various cholestatic disorders, including those of genetic origin. — through study completion, an average of 2 years
  Changes in the hepatobiliary excretion kinetics of 11C-CSar between patients and healthy

Trial sites (1)

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