Development of a Novel Nonpeptidic 18F-Labeled Radiotracer for in Vivo Imaging of Oxytocin Receptors with Positron Emission Tomography

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• 作者：Barbara Wenzel ; Jan Mollitor ; Winnie Deuther-Conrad ; Sladjana Dukic-Stefanovic ; Mathias Kranz ; Chrysoula Vraka ; Rodrigo Teodoro ; Robert Günther ; Cornelius K. Donat ; Friedrich-Alexander Ludwig ; Steffen Fischer ; Rene Smits ; Wolfgang Wadsak ; Markus Mitterhauser ; Jörg Steinbach ; Alexander Hoepping ; Peter Brust
• 刊名：Journal of Medicinal Chemistry
• 出版年：2016
• 出版时间：March 10, 2016
• 年：2016
• 卷：59
• 期：5
• 页码：1800-1817
• 全文大小：614K
• ISSN：1520-4804

文摘

With the aim of imaging and quantification of oxytocin receptors (OTRs) in living brain using positron emission tomography (PET), we developed a ¹⁸F-labeled small molecule radiotracer and investigated its in vivo pharmacokinetics in mice and pig. [¹⁸F]6b (K_D = 12.3 nM) was radiolabeled by a two-step procedure using a microwave system with radiochemical yields of 26.9 ± 4.7%. Both organ distribution and small animal PET studies revealed limited brain uptake of [¹⁸F]6b in mouse (mean SUV of 0.04 at 30 min pi). Besides, significant radioactivity uptake in the pituitary gland was observed (SUV of 0.7 at 30 min pi). In a dynamic PET study in one piglet, we detected a higher uptake of [¹⁸F]6b in the olfactory bulb (SUV of 0.34 at 30 min pi) accompanied by a low uptake in the whole brain. In vitro autoradiographic studies on porcine brain sections indicated interaction of [¹⁸F]6b with several off-target receptors.