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

A new PET ligand, 3-fluoro-5-(2-(2- ¹⁸F-(fluoromethyl)-thiazol-4-yl)ethynyl)benzonitrile ( ¹⁸F-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 ¹⁸F-SP203 binding in the brain. Nine healthy subjects were injected with ¹⁸F-SP203 using a bolus plus constant infusion for 300min. A single ratio of bolus-to-constant infusion (the activity of bolus equaled to that of infusion over 219min) was applied to all subjects to achieve equilibrium in approximately 120min. 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 ¹⁸F-SP203 in arterial plasma at 120min, and the kinetic method calculated V _T by a two-tissue compartment model using brain and plasma dynamic data from 0 to 120min. 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 ¹⁸F-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 ¹⁸F-SP203, the equilibrium method is more efficient because it requires much less data.