کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8457659 | 1548817 | 2018 | 31 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
A new method measuring the interaction of radiotracers with the human P-glycoprotein (P-gp) transporter
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کلمات کلیدی
MRP-1TQDMDCKIITariquidarMadin-Darby canine kidney cell lineMDR1ABCB1BcrpAUC - AUCEfflux transporter - انتقال دهنده خروجیPositron emission tomography - توموگرافی گسیل پوزیترونPET tracer - ردیاب PETarea under the curve - منطقه تحت منحنیwildtype - نوع وحشیVera - وراVerapamil - وراپامیلPET - پتbreast cancer resistance protein - پروتئین مقاومت به سرطان سینه
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
In drug development, biomarkers for cerebral applications have a lower success rate compared to cardiovascular drugs or tumor therapeutics. One reason is the missing blood brain barrier penetration, caused by the tracer's interaction with efflux transporters such as the P-gp (MDR1 or ABCB1). Aim of this study was the development of a reliable model to measure the interaction of radiotracers with the human efflux transporter P-gp in parallel to the radiolabeling process. LigandTracer® Technology was used with the wildtype cell line MDCKII and the equivalent cell line overexpressing human P-gp (MDCKII-hMDR1). The method was evaluated based on established PET tracers with known interaction with the human P-gp transporter and in nanomolar concentration (15â¯nM). [11C]SNAP-7941 and [18F]FE@SNAP were used as P-gp substrates by comparing the real-time model with an uptake assay and μPET images. [11C]DASB [11C]Harmine, [18F]FMeNER,[18F]FE@SUPPY and [11C]Me@HAPTHI were used as tracers without interactions with P-gp in vitro. However, [11C]Me@HAPTHI shows a significant increase in SUV levels after blocking with Tariquidar. The developed real-time kinetic model uses directly PET tracers in a compound concentration, which is reflecting the in vivo situation. This method may be used at an early stage of radiopharmaceutical development to measure interactions to P-gp before conducting animal experiments.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Nuclear Medicine and Biology - Volume 60, May 2018, Pages 29-36
Journal: Nuclear Medicine and Biology - Volume 60, May 2018, Pages 29-36
نویسندگان
Chrysoula Vraka, Monika Dumanic, Teresa Racz, Florian Pichler, Cecile Philippe, Theresa Balber, Eva-Maria Klebermass, Karl-Heinz Wagner, Marcus Hacker, Wolfgang Wadsak, Markus Mitterhauser,