Kinetic analysis of the metabotropic glutamate subtype 5 tracer [18F]FPEB in bolus and bolus-plus-constant-infusion studies in humans

[¹⁸F]FPEB is a positron emission tomography tracer which, in preclinical studies, has shown high specificity and selectivity toward the metabotropic glutamate receptor 5 (mGluR5). It possesses the potential to be used in human studies to evaluate mGluR5 function in a range of neuropsychiatric disorders, such as anxiety and Fragile X syndrome. To define optimal scan methodology, healthy human subjects were scanned for 6 hours following either a bolus injection (n=5) or bolus-plus-constant-infusion (n=5) of [¹⁸F]FPEB. Arterial blood samples were collected and parent fraction measured by high-performance liquid chromatography (HPLC) to determine the metabolite-corrected plasma input function. Time activity curves were extracted from 13 regions and fitted by various models to estimate V_T and BP_ND. [¹⁸F]FPEB was well fitted by the two-tissue compartment model, MA1 (t*=30), and MRTM (using cerebellum white matter as a reference). Highest V_T values were observed in the anterior cingulate and caudate, and lowest V_T values were observed in the cerebellum and pallidum. For kinetic modeling studies, V_T and BP_ND were estimated from bolus or bolus-plus-constant-infusion scans as short as 90 minutes. Bolus-plus-constant-infusion of [¹⁸F]FPEB reduced intersubject variability in V_T and allowed equilibrium analysis to be completed with a 30-minute scan, acquired 90–120 minutes after the start of injection.