Design and evaluation of a novel trifluorinated imaging agent for assessment of bile acid transport using fluorine magnetic resonance imaging.
Design and evaluation of a novel trifluorinated imaging agent for assessment of bile acid transport using fluorine magnetic resonance imaging.
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DOI：
10.1002/jps.24131
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发表时间：
2014-11
影响因子：
3.8
通讯作者：
Polli, James E.
中科院分区：
文献类型：
--
作者：
Vivian, Diana;Cheng, Kunrong;Khurana, Sandeep;Xu, Su;Dawson, Paul A.;Raufman, Jean-Pierre;Polli, James E.
关键词：
在此之前，我们开发了一种三氟化胆汁酸，CA-lys-TFA，目的是使用19 F磁共振成像（MRI）无创评估体内胆汁酸转运。CA-lys-TFA在小鼠胆囊中成功成像，但在体外易受胆酰甘氨酸水解酶（CGH）（一种在末端回肠和结肠中发现的细菌胆汁酸解偶联酶）的解偶联。本研究的目的是开发一种新的抗CGH去结合的三氟胆汁酸。CA-SAR-TFMA的设计，合成，并在体外运输性能，稳定性，成像性能，其差异积累在正常小鼠的胆囊中的能力进行了测试，与已知受损的胆汁酸转运（缺乏顶端钠依赖性胆汁酸转运蛋白，ASBT）的小鼠相比。CA-sar-TFMA是ASBT和Na+/牛磺胆酸盐共转运多肽的有效抑制剂和底物。在所有检测条件下（包括存在CGH），稳定性均有利。CA-SAR-TFMA成功成像，并在野生型小鼠胆囊中的浓度比Asbt缺陷小鼠高16.1倍。我们的研究结果支持使用MRI与CA-SAR-TFMA作为一种非侵入性方法来评估体内胆汁酸转运的潜力。
Previously, we developed a trifluorinated bile acid, CA-lys-TFA, with the objective of noninvasively assessing bile acid transport in vivo using 19F magnetic resonance imaging (MRI). CA-lys-TFA was successfully imaged in the mouse gallbladder, but was susceptible to deconjugation in vitro by choloylglycine hydrolase (CGH), a bacterial bile acid deconjugating enzyme found in the terminal ileum and colon. The objective of the present study was to develop a novel trifluorinated bile acid resistant to deconjugation by CGH. CA-sar-TFMA was designed, synthesized, and tested for in vitro transport properties, stability, imaging properties, and its ability to differentially accumulate in the gallbladders of normal mice, compared with mice with known impaired bile acid transport (deficient in the apical sodium-dependent bile acid transporter, ASBT). CA-sar-TFMA was a potent inhibitor and substrate of ASBT and the Na+/taurocholate cotransporting polypeptide. Stability was favorable in all conditions tested, including the presence of CGH. CA-sar-TFMA was successfully imaged and accumulated at 16.1-fold higher concentrations in gallbladders from wild-type mice compared with those from Asbt-deficient mice. Our results support the potential of using MRI with CA-sar-TFMA as a noninvasive method to assess bile acid transport in vivo.
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影响因子：
--
作者：
Dawson, Paul A
通讯作者：
Dawson, Paul A
影响因子：
4.6
作者：
Kolhatkar, Vidula;Polli, James E.
通讯作者：
Polli, James E.
DOI：
10.1097/00042737-199602000-00005
发表时间：
1996-02-01
影响因子：
2.1
作者：
Brydon, WG;Nyhlin, H;Merrick, MV
通讯作者：
Merrick, MV
影响因子：
3.7
作者：
Balakrishnan, A;Sussman, DJ;Polli, JE
通讯作者：
Polli, JE
影响因子：
4.8
作者：
Dawson, PA;Haywood, J;Parks, JS
通讯作者：
Parks, JS