Quantification of metabotropic glutamate subtype 5 receptors in the brain by an equilibrium method using 18F-SP203

Abstract A new PET ligand, 3-fluoro-5-(2-(2- 18 F-(fluoromethyl)-thiazol-4-yl)ethynyl)benzonitrile ( 18 F-SP203) can quantify metabotropic glutamate subtype 5 receptors (mGluR5) in human brain by a bolus injection and kinetic modeling. As an alternative approach to a bolus injection, binding can simply be measured as a ratio of tissue to metabolite-corrected plasma at a single time point under equilibrium conditions achieved by administering the radioligand with a bolus injection followed by a constant infusion. The purpose of this study was to validate the equilibrium method as an alternative to the standard kinetic method for measuring 18 F-SP203 binding in the brain. Nine healthy subjects were injected with 18 F-SP203 using a bolus plus constant infusion for 300 min. A single ratio of bolus-to-constant infusion (the activity of bolus equaled to that of infusion over 219 min) was applied to all subjects to achieve equilibrium in approximately 120 min. As a measure of ligand binding, we compared total distribution volume ( V T ) calculated by the equilibrium and kinetic methods in each scan. The equilibrium method calculated V T by the ratio of radioactivity in the brain to the concentration of 18 F-SP203 in arterial plasma at 120 min, and the kinetic method calculated V T by a two-tissue compartment model using brain and plasma dynamic data from 0 to 120 min. V T obtained via the equilibrium method was highly correlated with V T obtained via kinetic modeling. Inter-subject variability of V T obtained via the equilibrium method was slightly smaller than V T obtained via the kinetic method. V T obtained via the equilibrium method was ~ 10% higher than V T obtained via the kinetic method, indicating a small difference between the measurements. Taken together, the results of this study show that using the equilibrium method is an acceptable alternative to the standard kinetic method when using 18 F-SP203 to measure mGluR5. Although small differences in the measurements obtained via the equilibrium and kinetic methods exist, both methods consistently measured mGluR5 as indicated by the highly correlated V T values; the equilibrium method was slightly more precise, as indirectly measured by the smaller coefficient of variability across subjects. In addition, when using 18 F-SP203, the equilibrium method is more efficient because it requires much less data.