Measurement of extrastriatal D-2-like receptor binding with [C-11]FLB 457 - a test-retest analysis

[C-11]FLB 457 is a radioligand for positron emission tomography (PET) that possesses high affinity to D-2/D-3 receptors. It has been suggested to be u seful for quantification of low-density dopamine D-2 receptor populations, e.g. in cortical and limbic brain areas, We explored the reproducibility of five methods for measuring extrastriatal D-2-like receptor binding potenti al with [C-11]FLB 457. Seven healthy male volunteers were examined twice wi th [C-11]FLB 457 thigh specific radioactivity) on the same day, at least 3 h apart. Four brain areas, frontal cortex, nucleus thalamus, temporal corte x and cerebellar cortex, were examined. Binding potentials (BPs) were deriv ed from ii) a target to cerebellum distribution volume ratio, (2/3) two rev ersible reference tissue compartment models and (4) a transient equilibrium approach. For comparison, BP values were also calculated with the standard three-compartment kinetic model that does not assume a receptor-free refer ence region. The use of the standard three-compartment model did not result in reproducible BP estimates, The distribution volume (DV) ratio, referenc e tissue compartment models and the transient equilibrium method all had go od to excellent intraclass correlation coefficients (ICCs) in the studied b rain areas ranging from 0.56 to 0.93. Absolute variability was also relativ ely low, ranging from 5.3% to 10.4%. There were no marked differences in th e ICC or absolute and relative variability between the four methods based o n a reference tissue (cerebellum). In addition, we did not observe systemat ic differences in the BP between the first and the second scan. These data indicate that the reproducibility of the DV ratio, reference tissue models and the transient equilibrium method is good or excellent. However, each of these methods includes assumptions affecting their validity. Thus, the cho ice of method will be critically dependent on the purpose of the study.