title: Development of a Novel Nonpeptidic (18)F-Labeled Radiotracer for in Vivo Imaging of Oxytocin Receptors with Positron Emission Tomography.
abstract: With the aim of imaging and quantification of oxytocin receptors (OTRs) in living brain using positron emission tomography (PET), we developed a (18)F-labeled small molecule radiotracer and investigated its in vivo pharmacokinetics in mice and pig. [(18)F]6b (KD = 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 [(18)F]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 [(18)F]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 [(18)F]6b with several off-target receptors.
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research , Research Site Leipzig, Department of Neuroradiopharmaceuticals,, Permoserstr. 15, 04318 Leipzig, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Wenzel
authors.affiliation: ABX Advanced Biochemical Compounds GmbH , 01454 Radeberg, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Mollitor
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research , Research Site Leipzig, Department of Neuroradiopharmaceuticals,, Permoserstr. 15, 04318 Leipzig, Germany.
authors.forename: Winnie
authors.initials: W
authors.lastname: Deuther-Conrad
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research , Research Site Leipzig, Department of Neuroradiopharmaceuticals,, Permoserstr. 15, 04318 Leipzig, Germany.
authors.forename: Sladjana
authors.initials: S
authors.lastname: Dukic-Stefanovic
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research , Research Site Leipzig, Department of Neuroradiopharmaceuticals,, Permoserstr. 15, 04318 Leipzig, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Kranz
authors.affiliation: Radiopharmacy and Experimental Nuclear Medicine, Division of Nuclear Medicine, Medical University of Vienna , A-1090 Vienna, Austria.
authors.forename: Chrysoula
authors.initials: C
authors.lastname: Vraka
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research , Research Site Leipzig, Department of Neuroradiopharmaceuticals,, Permoserstr. 15, 04318 Leipzig, Germany.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Teodoro
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research , Research Site Leipzig, Department of Neuroradiopharmaceuticals,, Permoserstr. 15, 04318 Leipzig, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Günther
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research , Research Site Leipzig, Department of Neuroradiopharmaceuticals,, Permoserstr. 15, 04318 Leipzig, Germany.
authors.forename: Cornelius K
authors.initials: CK
authors.lastname: Donat
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research , Research Site Leipzig, Department of Neuroradiopharmaceuticals,, Permoserstr. 15, 04318 Leipzig, Germany.
authors.forename: Friedrich-Alexander
authors.initials: FA
authors.lastname: Ludwig
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research , Research Site Leipzig, Department of Neuroradiopharmaceuticals,, Permoserstr. 15, 04318 Leipzig, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Fischer
authors.affiliation: ABX Advanced Biochemical Compounds GmbH , 01454 Radeberg, Germany.
authors.forename: Rene
authors.initials: R
authors.lastname: Smits
authors.affiliation: Radiopharmacy and Experimental Nuclear Medicine, Division of Nuclear Medicine, Medical University of Vienna , A-1090 Vienna, Austria.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wadsak
authors.affiliation: Radiopharmacy and Experimental Nuclear Medicine, Division of Nuclear Medicine, Medical University of Vienna , A-1090 Vienna, Austria.
authors.forename: Markus
authors.initials: M
authors.lastname: Mitterhauser
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research , Research Site Leipzig, Department of Neuroradiopharmaceuticals,, Permoserstr. 15, 04318 Leipzig, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Steinbach
authors.affiliation: ABX Advanced Biochemical Compounds GmbH , 01454 Radeberg, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Hoepping
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research , Research Site Leipzig, Department of Neuroradiopharmaceuticals,, Permoserstr. 15, 04318 Leipzig, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Brust
mesh_terms: D000818:Animals; D001569:Benzodiazepines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000494:pharmacology; D001921:Brain / Q000000981:diagnostic imaging; D005462:Fluorine Radioisotopes / Q000032:analysis / Q000737:chemistry*; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D049268:Positron-Emission Tomography; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000494:pharmacology; D011849:Radioactive Tracers; D018045:Receptors, Oxytocin / Q000032:analysis* / Q000037:antagonists & inhibitors / Q000378:metabolism; D013552:Swine
chemical_list: D005462:Fluorine Radioisotopes; D011758:Pyrroles; D011849:Radioactive Tracers; D018045:Receptors, Oxytocin; C000609918:WAY-162720; D001569:Benzodiazepines