In vitro-in vivo drug transport correlation. (A) Chemical structures of radioligands investigated and used clinically. (B) Typical imaging data. Co-registered positron emission tomography (PET)-magnetic resonance imaging (MRI) images representing the k1 (the kinetic rate constant of the free ligand from the plasma to the free ligand compartment in the brain), obtained in human after intravenous injection of [11C]-befloxatone (left) and [18F]-F-A-85380 (right). The PET images representing the k1 were acquired as follows. The PET image obtained at 1 minute post-injection (mean value between 30 and 90 s) is considered independent of receptor binding. This image (in Bq/mL) is corrected from the vascular fraction (Fv in Bq/mL, considered as 4% of the total blood concentration at 1 minute) and divided by the arterial plasma input function (AUC0-1 minute (area under curve) of the plasma concentration, in Bq × Minutes/mL). The resulting parametric image, expressed in min-1, represents an index of the k1 parameter of the radiotracer. (C)In vivo distribution volume (DV) as a function of the in vitro Pe-in (permeability from apical to basolateral compartment)/Pe-out (permeability from basal to apical compartment) ratio (Q). The regression line was calculated, and correlation was estimated by the two-tailed non-parametric Spearman test.
Tsaioun et al. BMC Neurology 2009 9(Suppl 1):S1 doi:10.1186/1471-2377-9-S1-S1