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We recently developed a two-compartment, two-parameter tracer kinetic model to estimate the in vivo ligand transport rate ( K 1 ) and distribution volume (DV) for the benzodiazepine antagonist [ 11 C]flumazenil (FMZ) as measured by positron emission tomography (PET). The aim of the present study was to validate that this simplified model provides a stable measure of regional benzodiazepine receptor availability even when ligand delivery is altered. Six young normal volunteers underwent two PET studies subsequent to intravenous injections of [ 11 C]FMZ. Each FMZ study was immediately preceded by measurements of CBF following injection of [ 15 O]water. One set of scans (water/FMZ) was acquired under resting conditions and the other set during audiovisual stimulation. Six additional volunteers underwent two FMZ studies under identical resting conditions. Parametric images were analyzed and a comparison of test-retest studies in the stimulation group revealed a significant increase of CBF and K 1  of FMZ in the occipital cortex evoked by visual activation, whereas no regional changes were noted for the DV of FMZ. No significant changes were noted for either K 1  or DV of FMZ when comparing studies in the rest-rest setting. The results indicate that the use of a simple two-compartment model for the tracer kinetic analysis of [ 11 C]FMZ makes it possible to separate high-affinity binding from altered radioligand delivery to the human brain.

Differentiation of Radioligand Delivery and Binding in the Brain: Validation of a Two-Compartment Model for [11C]Flumazenil

Differentiation of Radioligand Delivery and Binding in the Brain: Validation of a Two-Compartment Model for [¹¹C]Flumazenil