کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10586549 | 981393 | 2010 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Synthesis and in vivo evaluation of [11C]tariquidar, a positron emission tomography radiotracer based on a third-generation P-glycoprotein inhibitor
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Synthesis and in vivo evaluation of [11C]tariquidar, a positron emission tomography radiotracer based on a third-generation P-glycoprotein inhibitor Synthesis and in vivo evaluation of [11C]tariquidar, a positron emission tomography radiotracer based on a third-generation P-glycoprotein inhibitor](/preview/png/10586549.png)
چکیده انگلیسی
The aim of this study was to develop a positron emission tomography (PET) tracer based on the dual P-glycoprotein (P-gp) breast cancer resistance protein (BCRP) inhibitor tariquidar (1) to study the interaction of 1 with P-gp and BCRP in the blood-brain barrier (BBB) in vivo. O-Desmethyl-1 was synthesized and reacted with [11C]methyl triflate to afford [11C]-1. Small-animal PET imaging of [11C]-1 was performed in naïve rats, before and after administration of unlabeled 1 (15 mg/kg, n = 3) or the dual P-gp/BCRP inhibitor elacridar (5 mg/kg, n = 2), as well as in wild-type, Mdr1a/b(â/â), Bcrp1(â/â) and Mdr1a/b(â/â)Bcrp1(â/â) mice (n = 3). In vitro autoradiography was performed with [11C]-1 using brain sections of all four mouse types, with and without co-incubation with unlabeled 1 or elacridar (1 μM). In PET experiments in rats, administration of unlabeled 1 or elacridar increased brain activity uptake by a factor of 3-4, whereas blood activity levels remained unchanged. In Mdr1a/b(â/â), Bcrp1(â/â) and Mdr1a/b(â/â)Bcrp1(â/â) mice, brain-to-blood ratios of activity at 25 min after tracer injection were 3.4, 1.8 and 14.5 times higher, respectively, as compared to wild-type animals. Autoradiography showed approximately 50% less [11C]-1 binding in transporter knockout mice compared to wild-type mice and significant displacement by unlabeled elacridar in wild-type and Mdr1a/b(â/â) mouse brains. Our data suggest that [11C]-1 interacts specifically with P-gp and BCRP in the BBB. However, further investigations are needed to assess if [11C]-1 behaves in vivo as a transported or a non-transported inhibitor.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 18, Issue 15, 1 August 2010, Pages 5489-5497
Journal: Bioorganic & Medicinal Chemistry - Volume 18, Issue 15, 1 August 2010, Pages 5489-5497
نویسندگان
Florian Bauer, Claudia Kuntner, Jens P. Bankstahl, Thomas Wanek, Marion Bankstahl, Johann Stanek, Severin Mairinger, Bernd Dörner, Wolfgang Löscher, Markus Müller, Thomas Erker, Oliver Langer,