کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5528958 1548822 2017 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
[11C]PF-3274167 as a PET radiotracer of oxytocin receptors: Radiosynthesis and evaluation in rat brain
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
[11C]PF-3274167 as a PET radiotracer of oxytocin receptors: Radiosynthesis and evaluation in rat brain
چکیده انگلیسی

IntroductionOxytocin plays a major role in the regulation of social interactions in mammals by interacting with the oxytocin receptor (OTR) expressed in the brain. Furthermore, the oxytocin system appears as a possible therapeutic target in autism spectrum disorders and other psychiatric troubles, justifying current pharmacological researches. Since no specific PET radioligand is currently available to image OTR in the brain, the aim of this study was to radiolabel the specific OTR antagonist PF-3274167 and to evaluate [11C]PF-3274167 as a potential PET tracer for OTR in rat brains.Methods[11C]PF-3274167 was prepared via the O-methylation of its desmethyl precursor with [11C]methyl iodide. The lipophilicity of the radioactive compound was evaluated by measuring the n-octanol-buffer partition coefficient (logD). Autoradiography experiments were performed on rat brain tissue to evaluate the in vitro distribution of the [11C]PF-3274167. MicroPET experiments were conducted with and without pre-injection of ciclosporin in order to evaluate the influence of the P-glycoprotein (P-gp) on the brain uptake.Results[11C]PF-3274167 was synthesized with high radiochemical and chemical purities (> 95%) and good specific activity. The measured logD was 1.93. In vitro, [11C]PF-3274167 did not show any evidence of specific binding to OTR. PET imaging showed that [11C]PF-3274167 uptake in rat brain was very low in basal conditions but increased significantly after the administration of ciclosporin, suggesting that it is a substrate of the P-gp. In the ciclosporin-pre-injected rat, however, [11C]PF-3274167 distribution did not match with the known distribution of OTR in rats.Conclusion[11C]PF-3274167 is not a suitable tracer for imaging of OTR in rat brain, probably because of a too low affinity for this receptor in addition to a poor brain penetration.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Nuclear Medicine and Biology - Volume 55, December 2017, Pages 1-6
نویسندگان
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