In vivo study of biodistribution and specific binding of [18 F] DPA-714, a traslocator protein-specific (TSPO) radioligand, in mice with microPET-CT.

Background: Development of PET radioligands for TSPO is of relevance for imaging inflammatory processes in brain and peripheral tissues as well as for a better understanding of the role of this protein in steroidogenesis, apoptosis and cells proliferation. [18F]DPA-714 is a new TSPO radioligand recently characterized in vivo with PET in normal primates and with microPET in rat models of neuroinflammation. The in vivo biodistribution and specific binding of [18F]DPA-714 have never been reported in mice, while limited data are available in other species. Murine biodistribution of DPA-714 could be of interest when studies of normal and/or transgenic mice and/or of involvement of peripheral TSPO are envisaged. The aim of this study was to characterize in vivo with microPET-CT the biodistribution and specific binding of [18F]DPA-714 in mice. Methods: We successfully performed the radiosynthesis of [18F]DPA-714 starting from the tosyloxy-derivative with a specific activity comprised between 294-60 GBq/?mol, according to the literature. The in vivo binding and biodistribution of [18F]DPA-714 were determined in 8-9 weeks C57BL mice (weight : 30 to 20g; anesthesia: intra-peritoneal administration of ketamine (100 mg/kg) -xylazine (10mg/kg). Dynamic PET acquisition was performed using the ?PET-CT GE Explore Vista (spatial resolution: PET=1 mm; CT=50 ?m). A total of six 10 min frames were acquired starting 5 min after radiotracer injection. Mice were positioned with the abdomen-thorax or brain centered in the FOV. Inhibition studies were conducted to evaluate the specificity of radioligand binding by injection of unlabeled DPA-714 (1mg/kg) 40 minutes after radiotracer injection (displacement) or 10 minutes prior to injection (presaturation). Parametric images of SUV (standard uptake value) were obtained and ROIs defined for lungs, heart, spleen, kidney and brain. Results: After [18F]DPA-714 injection, high radioactivity concentration was found in lungs, heart, kidney and spleen (fig 1, left). ROI analysis showed that at 30 minutes post [18F]DPA-714 injection, SUV values were higher in the lung and spleen followed by the kidney and the heart. At 60 min, SUV values were higher in spleen and kidney, followed by lung and heart. No or negligible levels of radioactivity were observed in the brain. Displacement and pre-treatment with unlabelled compound inhibited the uptake of [18F]DPA-714 in the lung and heart and, to a lesser extent, in the spleen and kidney. In later scans the radioactivity was redistributed to the intestine and to the renal medulla. Comments: These preliminary results suggest that [18F]DPA-714 can allow to image TSPO in vivo in mice. Biodistribution of [18F]DPA-714 follows the well known distribution of TSPO receptors in brain and peripheral tissues. Specific binding was higher in the lung and heart. Non specific binding and/or radioactive metabolites are present in the spleen and mostly in the kidneys, thus limiting the study of TSPO in these two latter peripheral organs. Further studies are required to evaluate [18F]DPA-714 peripheral metabolites.