11C-cholylsarcosine(University of Aarhus)(11C-cholylsarcosine(University of Aarhus))

概要

基本信息

药物类型

小分子化药、诊断用放射药物

别名

11C-CSAR

靶点-

作用方式

增强剂

作用机制

PET imaging(正电子发射断层成像术增强剂)

治疗领域

消化系统疾病其他疾病

在研适应症-

非在研适应症

原发性硬化性胆管炎原发性胆汁性胆管炎

原研机构

University of Aarhus

在研机构-

非在研机构

University of Aarhus

权益机构-

最高研发阶段无进展临床1期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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关联

2

项与 11C-cholylsarcosine(University of Aarhus) 相关的临床试验

EUCTR2016-004031-20-DK

/ Not yet recruiting临床1/2期IIT

Determination of radiation dose for the bile acid tracer 11C-CSar in humans

开始日期2017-02-20

申办/合作机构

Århus Universitetshospital

NCT01879735

/ Completed临床1期IIT

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

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.

开始日期2013-06-01

申办/合作机构

University of Aarhus

100 项与 11C-cholylsarcosine(University of Aarhus) 相关的临床结果

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100 项与 11C-cholylsarcosine(University of Aarhus) 相关的转化医学

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100 项与 11C-cholylsarcosine(University of Aarhus) 相关的专利（医药）

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2

项与 11C-cholylsarcosine(University of Aarhus) 相关的文献（医药）

2021-06-01·JHEP reports : innovation in hepatology

Hepatic bile acid transport increases in the postprandial state: A functional 11C-CSar PET/CT study in healthy humans

Article

作者: Ørntoft, Nikolaj W ; Gormsen, Lars C ; Keiding, Susanne ; Sørensen, Michael ; Ott, Peter ; Munk, Ole L

BACKGROUND & AIMS:

It is not known how hepatic bile acids transport kinetics changes postprandially in the intact liver. We used positron emission tomography (PET)/computed tomography (CT) with the tracer [N-methyl-¹¹C]cholylsarcosine (¹¹C-CSar), a synthetic sarcosine conjugate of cholic acid, to quantify fasting and postprandial hepatic bile acid transport kinetics in healthy human participants.

METHODS:

Six healthy human participants underwent dynamic liver ¹¹C-CSar PET/CT (60 min) during fasting and from 15 min after ingestion of a standard liquid meal. Hepatobiliary secretion kinetics of ¹¹C-CSar was calculated from PET data, blood samples (arterial and hepatic venous) and hepatic blood flow measured using indocyanine green infusion.

RESULTS:

In the postprandial state, hepatic blood perfusion increased on average by 30% (p <0.01), and the flow-independent hepatic intrinsic clearance of ¹¹C-CSar from blood into bile increased by 17% from 1.82 (range, 1.59-2.05) to 2.13 (range, 1.75-2.50) ml blood/min/ml liver tissue (p = 0.042). The increased intrinsic clearance of ¹¹C-CSar was not caused by changes in the basolateral clearance efficacy of ¹¹C-CSar but rather by an upregulated apical transport, as shown by an increase in the rate constant for apical secretion of ¹¹C-CSar from hepatocyte to bile from 0.40 (0.25-0.54) min^-1 to 0.67 (0.36-0.98) min^-1 (p = 0.03). This resulted in a 33% increase in the intrahepatic bile flow (p = 0.03).

CONCLUSIONS:

The rate constant for the transport of bile acids from hepatocytes into biliary canaliculi and the bile flow increased significantly in the postprandial state. This reduced the mean ¹¹C-CSar residence time in the hepatocytes.

LAY SUMMARY:

Bile acids are important for digestion of dietary lipids including vitamins. We examined how the secretion of bile acids by the liver into the intestines changes after a standard liquid meal. The transport of bile acids from liver cells into bile and bile flow was increased after the meal.

2017-08-01·Journal of hepatology1区 · 医学

Hepatobiliary transport kinetics of the conjugated bile acid tracer 11C-CSar quantified in healthy humans and patients by positron emission tomography

1区 · 医学

Article

作者: Munk, Ole Lajord ; Frisch, Kim ; Sørensen, Michael ; Keiding, Susanne ; Ott, Peter ; Ørntoft, Nikolaj Worm

BACKGROUND & AIMS:

Hepatobiliary secretion of bile acids is an important liver function. Here, we quantified the hepatic transport kinetics of conjugated bile acids using the bile acid tracer [N-methyl-¹¹C]cholylsarcosine (¹¹C-CSar) and positron emission tomography (PET).

METHODS:

Nine healthy participants and eight patients with varying degrees of cholestasis were examined with ¹¹C-CSar PET and measurement of arterial and hepatic venous blood concentrations of ¹¹C-CSar.

RESULTS:

Results are presented as median (range). The hepatic intrinsic clearance was 1.50 (1.20-1.76) ml blood/min/ml liver tissue in healthy participants and 0.46 (0.13-0.91) in patients. In healthy participants, the rate constant for secretion of ¹¹C-CSar from hepatocytes to bile was 0.36 (0.30-0.62)min^-1, 20 times higher than the rate constant for backflux from hepatocytes to blood (0.02, 0.005-0.07min^-1). In the patients, rate constant for transport from hepatocyte to bile was reduced to 0.12 (0.006-0.27)min^-1, 2.3times higher than the rate constant for backflux to blood (0.05, 0.04-0.09). The increased backflux did not fully normalize exposure of the hepatocyte to bile acids as mean hepatocyte residence time of ¹¹C-CSar was 2.5 (1.6-3.1)min in healthy participants and 6.4 (3.1-23.7)min in patients. The rate constant for transport of ¹¹C-CSar from intrahepatic to extrahepatic bile was 0.057 (0.023-0.11)min^-1 in healthy participants and only slightly reduced in patients 0.039 (0.017-0.066).

CONCLUSIONS:

This first in vivo quantification of individual steps involved in the hepatobiliary secretion of a conjugated bile acid in humans provided new insight into cholestatic disease.

LAY SUMMARY:

Positron emission tomography (PET) using the radiolabelled bile acid (¹¹C-CSar) enabled quantification of the individual steps of the hepatic transport of bile acids from blood to bile in man. Cholestasis reduced uptake and secretion and increased backflux to blood. These findings improve our understanding of cholestatic liver diseases and may support therapeutic decisions.

CLINICAL TRIAL REGISTRATION NUMBER:

The trial is registered at ClinicalTrials.gov (NCT01879735).

100 项与 11C-cholylsarcosine(University of Aarhus) 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
原发性硬化性胆管炎	临床1期	丹麦	University of Aarhus	2013-06-01
原发性胆汁性胆管炎	临床1期	丹麦	University of Aarhus	2013-06-01

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


EASL2019	N/A	-	6	11C-CSar (Fasting)	簾觸艱簾構糧網憲淵糧(簾構範餘夢壓蓋願簾壓) = 製憲壓壓築構構醖遞醖築範網遞遞艱觸願簾簾 (範繭構選構獵簾壓簾衊, 2.21 ~ 5.22) 更多	-	2019-04-11
				11C-CSar (Postprandial)	簾觸艱簾構糧網憲淵糧(簾構範餘夢壓蓋願簾壓) = 積鑰鑰鬱鑰簾觸鑰鑰構築範網遞遞艱觸願簾簾 (範繭構選構獵簾壓簾衊, 2.21 ~ 5.22) 更多
NCT03253276 \| NCT01879735 (Pubmed \| J Hepatol)	N/A	-	-	<sup>11</sup>C-CSar (Healthy participants)	獵蓋顧膚齋簾鹽網憲製(壓鬱餘蓋願選夢遞壓壓) = 鹹鹹築願壓鑰積獵憲鏇遞憲觸選範築醖糧夢壓 (製積鏇遞憲夢糧醖鬱鬱, 1.20 ~ 1.76)	-	2017-08-01
				<sup>11</sup>C-CSar (Patients with varying degrees of cholestasis)	獵蓋顧膚齋簾鹽網憲製(壓鬱餘蓋願選夢遞壓壓) = 鬱艱齋齋淵範製鬱範夢遞憲觸選範築醖糧夢壓 (製積鏇遞憲夢糧醖鬱鬱, 0.13 ~ 0.91)
NCT01879735 (CTgov)	临床1期	原发性硬化性胆管炎 \| 原发性胆汁性胆管炎	22	11C-CSar+ICG (Infusion Method)	選窪觸願廠範獵鏇餘廠 = 壓糧糧壓遞醖糧艱窪選簾範簾廠醖繭獵鑰獵範 (遞廠廠蓋鹹夢襯觸鬱簾, 觸願製蓋壓範顧選網壓 ~ 簾淵鏇膚壓醖鹽觸遞築)	-	2015-02-23
				11C-CSar+ICG (ICG's Effect on 11C-CSar Transport)	積窪糧築網觸觸簾鬱憲(膚蓋餘繭鹹餘遞憲衊鑰) = 蓋壓簾鏇築蓋獵簾構構鬱襯膚衊醖鏇淵膚餘選 (窪餘淵淵糧憲築艱獵簾, 憲築網憲選獵淵願膚壓 ~ 範廠鑰選憲壓鬱鏇鏇選) 更多