11C-SSR180575 evaluated under normal and pathological conditions in nonhuman primate brain

356 Objectives SSR180575 is a selective antagonist of the TSPO with potential neuroprotective effects at pharmacological doses. The carbon-11 labelled SSR180575 ligand was evaluated in the macaca fascicularis before and after excitotoxic striatal lesion. Methods Dynamic acquisitions of 120min (FOCUS220, Siemens) were performed under propofol anaesthesia starting at radioligand injection. Each animal underwent a baseline and a retest scan followed by a presaturation and a displacement study by PK11195. An excitotoxic lesion was then induced in three monkeys in the left striatum by stereotactic quinolinate injections. The animals were imaged at day 2, 9, 16, 23 and 46 after the lesion, and at the end of the study sacrificed for histological analysis. Brain PET data were coregistered to the corresponding T2-weighted MR images acquired on a 7T Varian scanner at different time points during the follow up study. Time activity curves extracted from different brain regions were expressed in SUV by normalizing for injected dose and body weight, and kinetic modelling was performed using the fitted individual arterial input functions. Results Before lesion, a specific and reversible binding of 11C-SSR180575 was observed homogeneously all over the brain. Despite this ubiquituous distribution of the tracer in the normal condition, a clear increase in binding was observed in the quinolinate injected striatum up to 2 weeks after lesion, reaching a maximum contrast at nine days as shown by SUV time activity curves and by modelling using the Ichise invasive model. Conclusions Ongoing in vivo/post-mortem correlations between the PET data and various immunohistological stained sections for GFAP, Iba1, CD68, TSPO, NeuN, should yield complementary information regarding the cellular events associated with this increased binding. Nevertheless, the present study already reveals a promising specificity and sensitivity of 11C-SSR180575 for the TSPO in vivo. Research Support Thominiaux et al., DOI: 10.1002/jlcr.179