Serotonin 5-HT3 receptors are involved in various brain functions including as an emesis target during cancer chemotherapy. We report here the development of (S)-2,3-dimethoxy-5-(3′-[18F]fluoropropyl)-N-(1-azabicyclo[2.2.2]oct-3-yl)benzamide ([18F]fesetron) as a potential PET imaging agent for serotonin 5-HT3 receptors. By radiolabeling((S)-2,3-dimethoxy-5-(3′-tosyloxypropyl)-N-(1-azabicyclo[2.2.2]oct-3-yl)benzamide) with fluorine-18, (S)-[18F]fesetron was obtained in 5 to 10% decay-corrected yields and with specific activities >74 GBq/μmol at the end of radiosynthesis. PET imaging in rats showed low uptake of [18F]fesetron in the brain with retention of binding in the striatal and cerebellar regions. Using colliculi as a reference region, ratios were 3.4 for striata and 2.5 for cerebellum. Ex vivo brain PET analysis displayed binding of [18F]fesetron in the hippocampus, striatum and cerebellar regions. Cerebellar regions corresponded to area postrema and nucleus tract solitaris known to contain 5-HT3 receptors. Dorsal hippocampus showed the highest uptake with ratio of >17 with respect to colliculi, while area postrema and striata had ratios of >10. Thus, [18F]fesetron exhibited a unique binding profile to rat brain regions known to contain significant amounts of serotonin 5-HT3 receptors. However, the very low brain uptake limits its usefulness as a PET radiotracer in this animal model.

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Objectives:To evaluate the utility of tracheal aspirates in suspected pneumonia in intubated neonates and to measure the burden of antibiotic use associated with a positive tracheal aspirate culture.Design:Retrospective cohort study between January 2016 and December 2017.Setting:A level IV neonatal intensive care unit (NICU).Patients:Intubated patients with a tracheal aspirate culture.Methods:Data on temporally associated clinical measures of illness, laboratory and radiographic testing, and clinical demographic information were analyzed.Results:Positive tracheal aspirate cultures were associated with lower birth weight and a normal immature to total neutrophil ratio (I/T ratio). Positive tracheal aspirates were not significantly associated with clinical, laboratory, or radiographic markers used in clinical practice to screen for infection. Despite the lack of positive clinical associations, a positive tracheal aspirate culture was associated with increased risk of prolonged antibiotic exposure.Conclusion:These findings suggest that positive tracheal aspirates do not always represent clinical infection and may result in unnecessary antibiotic exposure.

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