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

[F-18]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 [F-18]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 BPND. [F-18]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 BPND were estimated from bolus or bolus-plus-constant-infusion scans as short as 90 minutes. Bolus-plus-constant-infusion of [F-18]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. Journal of Cerebral Blood Flow & Metabolism (2013) 33, 532-541; doi:10.1038/jcbfm.2012.195; published online 19 December 2012