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

靶点-

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

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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22

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

2021-06-01·JHEP Reports

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

Article

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

BACKGROUND & AIMSIt 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.METHODSSix 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.RESULTSIn 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).CONCLUSIONSThe 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 SUMMARYBile 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.

2012-05-01·Journal of Nuclear Medicine1区 · 医学

[N-Methyl-¹¹C]Cholylsarcosine, a Novel Bile Acid Tracer for PET/CT of Hepatic Excretory Function: Radiosynthesis and Proof-of-Concept Studies in Pigs

1区 · 医学

Article

作者: Frisch, Kim ; Jakobsen, Steen ; Sørensen, Michael ; Munk, Ole Lajord ; Keiding, Susanne ; Hofmann, Alan F ; Ott, Peter ; Alstrup, Aage K O

Excretion of conjugated bile acids into bile is an essential function of the liver, and impairment of canalicular bile acid secretion leads to cholestatic liver injury. However, hepatic excretory function cannot be quantified in vivo because of the lack of suitable methods. Cholylsarcosine is an analog of the endogenous bile acid conjugate cholylglycine and exhibits characteristics in vivo that led us to hypothesize that the (11)C-labeled form, that is, [N-methyl-(11)C]cholylsarcosine ((11)C-cholylsarcosine), would be a suitable PET tracer for quantification of hepatic excretory function.METHODSA method for radiosynthesis of (11)C-cholylsarcosine was developed involving (11)C-methylation of glycine followed by conjugation with cholic acid. Blood-to-liver uptake and liver-to-bile excretion were investigated in vivo by dynamic (11)C-cholylsarcosine PET/CT of 2 anesthetized pigs. In pig 1, a second dynamic (11)C-cholylsarcosine PET/CT examination was preceded by a high dose of the endogenous bile acid conjugate cholyltaurine to investigate possible inhibition of the transhepatocellular transport of (11)C-cholylsarcosine. In pig 2, a second (11)C-cholylsarcosine administration was given to determine the biodistribution of the tracer by means of 5 successive whole-body PET/CT recordings. Possible formation of (11)C-metabolites was investigated by analysis of blood and bile samples from a third pig.RESULTSThe radiochemical yield was 13% ± 3% (n = 7, decay-corrected) and up to 1.1 GBq of (11)C-cholylsarcosine was produced with a radiochemical purity greater than 99%. PET/CT studies showed rapid blood-to-liver uptake and liver-to-bile excretion of (11)C-cholylsarcosine, with radioactivity concentrations being more than 90 times higher in the bile ducts than in liver tissue. Cholyltaurine inhibited the transhepatocellular transport of (11)C-cholylsarcosine, indicating that the tracer is transported by one or more of the same hepatic transporters as cholyltaurine. (11)C-cholylsarcosine underwent an enterohepatic circulation and reappeared in liver tissue and bile ducts after approximately 70 min. There were no detectable (11)C-metabolites in the plasma or bile samples, indicating that the novel conjugated bile acid (11)C-cholylsarcosine was not metabolized in the liver or in the intestines. The effective absorbed dose of (11)C-cholylsarcosine was 4.4 μSv/MBq.CONCLUSIONWe have synthesized a novel conjugated bile acid analog, (11)C-cholylsarcosine, and PET/CT studies on anesthetized pigs showed that the hepatic handling of tracer uptake from blood and excretion into the bile was comparable to that for the endogenous bile acid cholyltaurine. This tracer may be valuable for future studies of normal and pathologic hepatic excretory functions in humans.

2010-11-01·European Journal of Pharmaceutics and Biopharmaceutics2区 · 医学

In vitro evaluation of liposomes containing bio-enhancers for the oral delivery of macromolecules

2区 · 医学

Article

作者: Gert Fricker ; Johannes Parmentier ; Felix J. Hartmann

The aim of this work was to develop a new type of liposomes containing bio-enhancers for oral delivery of hydrophilic macromolecules. The study focused on EPC/cholesterol-based formulations combined with TPGS 1000 and 400, cholylsarcosine (CS), cetylpyridinium chloride (CpCl) and stearylamine (SA) covering a broad range of different types of enhancers. Most of the tested liposomal formulations and enhancers showed neither influence on cell viability in the Alamar Blue® assay nor an increase in lactate dehydrogenase LDH release. But, at a concentration of 1 mM, CpCl exhibited a strong toxicity after 2 h, TPGS 1000 reduced the cell viability at the same concentration after 8h significantly. Only one liposomal formulation with 25% CpCl led to a decrease in viability to 60.0% after 8h at a total lipid concentration of 5 mM. In the Caco-2 Transwell® model, one formulation with 5% TPGS 400 improved the permeation of FITC-dextran 70 kDa 3.34 ± 0.62-fold, one with 10% CpCl 3.69 ± 0.67 and one with 10% CS and 2.5% SA 3.41 ± 0.51-fold without influencing the TER. Liposomes with 10% SA or 25% CpCl increased the permeation of FITC-dextran 29.02 ± 5.84, respectively 39.28 ± 2.10-fold, but led also to a strong reduction in the TER. Especially, the three formulations which enhanced the permeation of FITC-dextran around 3.5-fold without showing any cell toxicity or decrease in TER should be safe and effective candidates for the development of an oral delivery system for hydrophilic macromolecules.

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	蓋獵餘壓顧餘鏇顧獵鏇(壓蓋壓鏇簾鹹鑰蓋鏇範) = 選蓋淵襯憲艱齋範築簾構淵鑰遞簾衊網窪餘築 (膚顧顧艱夢廠願鑰淵築, 2.21 ~ 5.22) 更多	-	2019-04-11
				11C-CSar	蓋獵餘壓顧餘鏇顧獵鏇(壓蓋壓鏇簾鹹鑰蓋鏇範) = 鏇製鏇選襯糧遞獵夢獵構淵鑰遞簾衊網窪餘築 (膚顧顧艱夢廠願鑰淵築, 2.21 ~ 5.22) 更多
NCT03253276 \| NCT01879735 (Pubmed \| J Hepatol)	N/A	-	-	<sup>11</sup>C-CSar (Healthy participants)	膚衊鬱鏇鑰壓簾衊夢願(鹹顧膚憲蓋選齋顧窪鹽) = 鹹膚範積選醖觸遞餘壓觸鏇齋夢齋願壓鹹築鏇 (鏇繭範壓壓觸築醖夢蓋, 1.20 ~ 1.76)	-	2017-08-01
				<sup>11</sup>C-CSar (Patients with varying degrees of cholestasis)	膚衊鬱鏇鑰壓簾衊夢願(鹹顧膚憲蓋選齋顧窪鹽) = 淵鏇憲鹹鏇廠鬱衊遞蓋觸鏇齋夢齋願壓鹹築鏇 (鏇繭範壓壓觸築醖夢蓋, 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)	壓網壓繭製夢衊襯選網(憲繭憲蓋衊壓壓蓋鹽衊) = 艱廠繭選鑰製觸蓋鏇襯艱願築選壓憲醖艱積簾 (鏇襯積鏇範獵範構鬱糧, 襯淵簾鹹夢繭壓艱範網 ~ 積憲觸廠獵衊襯積窪襯)	-	2015-02-23
				11C-CSar+ICG (ICG's Effect on 11C-CSar Transport)	糧鏇製顧願夢艱淵鏇鏇(積膚遞構獵觸鹽遞廠鏇) = 範餘選醖願餘艱網製憲繭獵遞簾網襯鹹齋築鬱 (鑰夢鹹鏇積艱鑰壓憲觸, 鏇鑰鑰觸獵鹽鏇築齋遞 ~ 簾廠選壓積蓋蓋膚餘壓) 更多