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The in vivo kinetic behavior of [ 11 C]flumazenil ([ 11 C]FMZ), a non-subtype-specific central benzodiazepine antagonist, is characterized using compartmental analysis with the aim of producing an optimized data acquisition protocol and tracer kinetic model configuration for the assessment of [ 11 C]FMZ binding to benzodiazepine receptors (BZRs) in human brain. The approach presented is simple, requiring only a single radioligand injection. Dynamic positron emission tomography data were acquired on 18 normal volunteers using a 60- to 90-min sequence of scans and were analyzed with model configurations that included a three-compartment, four-parameter model, a three-compartment, three-parameter model, with a fixed value for free plus nonspecific binding; and a two-compartment, two-parameter model. Statistical analysis indicated that a four-parameter model did not yield significantly better fits than a three-parameter model. Goodness of fit was improved for three- versus two-parameter configurations in regions with low receptor density, but not in regions with moderate to high receptor density. Thus, a two-compartment, two-parameter configuration was found to adequately describe the kinetic behavior of [ 11 C]FMZ in human brain, with stable estimates of the model parameters obtainable from as little as 20–30 min of data. Pixel-by-pixel analysis yields functional images of transport rate ( K 1 ) and ligand distribution volume ( DV“), and thus provides independent estimates of ligand delivery and BZR binding.

journal of cerebral blood flow and metabolism

Compartmental Analysis of [<sup>11</sup>C]Flumazenil Kinetics for the Estimation of Ligand Transport Rate and Receptor Distribution Using Positron Emission Tomography

Compartmental Analysis of [11C]Flumazenil Kinetics for the Estimation of Ligand Transport Rate and Receptor Distribution Using Positron Emission Tomography

Compartmental Analysis of [¹¹C]Flumazenil Kinetics for the Estimation of Ligand Transport Rate and Receptor Distribution Using Positron Emission Tomography