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Evaluating Hepatobiliary Transport with 18F-Labeled Bile Acids: The Effect of Radiolabel Position and Bile Acid Structure on Radiosynthesis and In Vitro and In Vivo Performance
المؤلفون المشاركون
De Lombaerde, Stef
Kersemans, Ken
Neyt, Sara
Verhoeven, Jeroen
Vanhove, Christian
De Vos, Filip
المصدر
Contrast Media & Molecular Imaging
العدد
المجلد 2018، العدد 2018 (31 ديسمبر/كانون الأول 2018)، ص ص. 1-9، 9ص.
الناشر
Hindawi Publishing Corporation
تاريخ النشر
2018-04-23
دولة النشر
مصر
عدد الصفحات
9
التخصصات الرئيسية
الملخص EN
Introduction.
An in vivo determination of bile acid hepatobiliary transport efficiency can be of use in liver disease and preclinical drug development.
Given the increased interest in bile acid Positron Emission Tomography- (PET-) imaging, a further understanding of the impact of 18-fluorine substitution on bile acid handling in vitro and in vivo can be of significance.
Methods.
A number of bile acid analogues were conceived for nucleophilic substitution with [18F]fluoride: cholic acid analogues of which the 3-, 7-, or 12-OH function is substituted with a fluorine atom (3α-[18F]FCA; 7β-[18F]FCA; 12β-[18F]FCA); a glycocholic and chenodeoxycholic acid analogue, substituted on the 3-position (3β-[18F]FGCA and 3β-[18F]FCDCA, resp.).
Uptake by the bile acid transporters NTCP and OATP1B1 was evaluated with competition assays in transfected CHO and HEK cell lines and efflux by BSEP in membrane vesicles.
PET-scans with the tracers were performed in wild-type mice (n=3 per group): hepatobiliary transport was monitored and compared to a reference tracer, namely, 3β-[18F]FCA.
Results.
Compounds 3α-[18F]FCA, 3β-[18F]FGCA, and 3β-[18F]FCDCA were synthesized in moderate radiochemical yields (4–10% n.d.c.) and high radiochemical purity (>99%); 7β-[18F]FCA and 12β-[18F]FCA could not be synthesized and included further in this study.
In vitro evaluation showed that 3α-FCA, 3β-FGCA, and 3β-FCDCA all had a low micromolar Ki-value for NTCP, OATP1B1, and BSEP.
In vivo, 3α-[18F]FCA, 3β-[18F]FGCA, and 3β-[18F]FCDCA displayed hepatobiliary transport with varying efficiency.
A slight yet significant difference in uptake and efflux rate was noticed between the 3α-[18F]FCA and 3β-[18F]FCA epimers.
Conjugation of 3β-[18F]FCA with glycine had no significant effect in vivo.
Compound 3β-[18F]FCDCA showed a significantly slower hepatic uptake and efflux towards gallbladder and intestines.
Conclusion.
A set of 18F labeled bile acids was synthesized that are substrates of the bile acid transporters in vitro and in vivo and can serve as PET-biomarkers for hepatobiliary transport of bile acids.
نمط استشهاد جمعية علماء النفس الأمريكية (APA)
De Lombaerde, Stef& Kersemans, Ken& Neyt, Sara& Verhoeven, Jeroen& Vanhove, Christian& De Vos, Filip. 2018. Evaluating Hepatobiliary Transport with 18F-Labeled Bile Acids: The Effect of Radiolabel Position and Bile Acid Structure on Radiosynthesis and In Vitro and In Vivo Performance. Contrast Media & Molecular Imaging،Vol. 2018, no. 2018, pp.1-9.
https://search.emarefa.net/detail/BIM-1131492
نمط استشهاد الجمعية الأمريكية للغات الحديثة (MLA)
De Lombaerde, Stef…[et al.]. Evaluating Hepatobiliary Transport with 18F-Labeled Bile Acids: The Effect of Radiolabel Position and Bile Acid Structure on Radiosynthesis and In Vitro and In Vivo Performance. Contrast Media & Molecular Imaging No. 2018 (2018), pp.1-9.
https://search.emarefa.net/detail/BIM-1131492
نمط استشهاد الجمعية الطبية الأمريكية (AMA)
De Lombaerde, Stef& Kersemans, Ken& Neyt, Sara& Verhoeven, Jeroen& Vanhove, Christian& De Vos, Filip. Evaluating Hepatobiliary Transport with 18F-Labeled Bile Acids: The Effect of Radiolabel Position and Bile Acid Structure on Radiosynthesis and In Vitro and In Vivo Performance. Contrast Media & Molecular Imaging. 2018. Vol. 2018, no. 2018, pp.1-9.
https://search.emarefa.net/detail/BIM-1131492
نوع البيانات
مقالات
لغة النص
الإنجليزية
الملاحظات
Includes bibliographical references
رقم السجل
BIM-1131492
قاعدة معامل التأثير والاستشهادات المرجعية العربي "ارسيف Arcif"
أضخم قاعدة بيانات عربية للاستشهادات المرجعية للمجلات العلمية المحكمة الصادرة في العالم العربي
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