Biliary Excretion of Conjugated Bile Acids in Humans Measured by 11C-cholylsarcosine PET/CT

Study Overview
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Brief Summary
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We wish to develop a protocol for PET/CT examination of humans using the bile acid tracer 11C-cholylsarcosine. This is done by a series of PET/CT examinations of healthy humans and patients with cholestatic disorders.

Detailed Description
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The purpose of the study is the development of PET/CT protocols using 11C-CSar for human use. PET/CT methods developed in the pig studies are translated to studies in healthy humans and patients with cholestatic disorders. Dynamic PET/CT scans of the liver and biliary system are combined with measurements of tracer concentrations in a radial artery and a liver vein and measurements of hepatic blood flow by intravenous infusion of indocyanine green (ICG)/Ficks principle. Kinetic parameters from PET/CT measurements and invasive measurements are compared for validation of the PET estimated parameters and refinement of the PET modeling, if required.

Official Title
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Hepatic Transport of Conjugated Bile Acids in Humans Quantified by 11C-cholylsarcosine PET/CT

Conditions
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Cholestasis, Primary Sclerosing Cholangitis, Primary Biliary Cirrhosis

Intervention / Treatment
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* Drug: 11C-CSar
* Drug: ICG


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with cholestatic disorders and healthy subjects Exclusion Criteria: Body weight above 110 kg (catheterization problematic). Diabetes Pregnant or breast feeding women.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ICG's effect on 11C-CSar transport<br>Examine the effect of ICG on the kinetics of the hepatic transport of 11C-CSar. If no effect is seen on the kinetics, ICG will be used during the infusion method experiments. | Drug: 11C-CSar<br>* PET/CT recording with bile acid tracer 11C-cholylsarcosine used to evaluate the transport of bile acids.<br>* Other names: 11C-cholylsarcosine;Drug: ICG<br>* Infusion of indocyanine green prior and during the PET/CT scanning with the bile tracer 11C-CSar.<br>* Other names: indocyanine green;|
| Experimental: Infusion method<br>Determine wether bolus or constant infusion of 11C-CSar is optimal for the PET/CT scanning. If ICG does not affect the kinetics of 11C-CSar it will be used during these experiments to calculate hepatic blood flow. | Drug: 11C-CSar<br>* PET/CT recording with bile acid tracer 11C-cholylsarcosine used to evaluate the transport of bile acids.<br>* Other names: 11C-cholylsarcosine;Drug: ICG<br>* Infusion of indocyanine green prior and during the PET/CT scanning with the bile tracer 11C-CSar.<br>* Other names: indocyanine green;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants in Whom we Could Quantify Hepatic Transport of 11C-CSar |  | All measurements are performed in one day. |