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

摘要

With the aim of imaging and quantification of oxytocin receptors (OTRs) in living brain using positron emission tomography (PET), we developed a F-18-labeled small molecule radiotracer and investigated its in vivo pharmacokinetics in mice and pig. [F-18]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 [F-18]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 [F-18]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 [F-18]6b with several off-target receptors.