[¹⁸F]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, [¹⁸F]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 [¹⁸F]LW223 PET data. Adult male mice were injected with [¹⁸F]LW223 and varying concentrations of LW223 (0.003-0.55 mg/kg) to estimate V_ND of [¹⁸F]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. [¹⁸F]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 [¹⁸F]LW223 PET data, although its correlation with SUV_90-120min or V_Tapp allowed for [¹⁸F]LW223 brain PET data quantification in healthy animals while using simpler experimental and analytical approaches. [¹⁸F]LW223 has the required properties to become a successful TSPO PET radiotracer.