[ 18 F]LW223 has low non-displaceable binding in murine brain, enabling high sensitivity TSPO PET imaging

Neuroinflammation is associated with a number of brain diseases, making it a common feature of cerebral pathology. Among the best-known biomarkers for neuroinflammation in Positron Emission Tomography (PET) research is the 18 kDa translocator protein (TSPO). This study aims to investigate the binding kinetics of a novel TSPO PET radiotracer, [ 18 F]LW223, in mice and specifically assess its volume of non-displaceable binding ( V ND ) in brain as well as investigate the use of simplified analysis approaches for quantification of [ 18 F]LW223 PET data. Adult male mice were injected with [ 18 F]LW223 and varying concentrations of LW223 (0.003–0.55 mg/kg) to estimate V ND of [ 18 F]LW223. Dynamic PET imaging with arterial input function studies and radiometabolite studies were conducted. Simplified quantification methods, standard uptake values ( SUV) and apparent volume of distribution ( V Tapp ), were investigated. [ 18 F]LW223 had low V ND in the brain (<10% of total binding) and low radiometabolism (∼15–20%). The 2-tissue compartment model provided the best fit for [ 18 F]LW223 PET data, although its correlation with SUV 90–120min or V Tapp allowed for [ 18 F]LW223 brain PET data quantification in healthy animals while using simpler experimental and analytical approaches. [ 18 F]LW223 has the required properties to become a successful TSPO PET radiotracer.