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[ 18 F]MC225 has been developed as a weak substrate of P-glycoprotein (P-gp) aimed to measure changes in the P-gp function at the blood-brain barrier with positron emission tomography. This study evaluates [ 18 F]MC225 kinetics in non-human primates and investigates the effect of both scan duration and P-gp inhibition. Three rhesus monkeys underwent two 91-min dynamic scans with blood sampling at baseline and after P-gp inhibition (8 mg/kg tariquidar). Data were analyzed using the 1-tissue compartment model (1-TCM) and 2-tissue compartment model (2-TCM) fits using metabolite-corrected plasma as the input function and for various scan durations (10, 20, 30, 60, and 91 min). The preferred model was chosen according to the Akaike information criterion and the standard errors (%) of the estimated parameters. For the 91-min scan duration, the influx constant K  1 increased by 40.7% and the volume of distribution ( V  T ) by 30.4% after P-gp inhibition, while the efflux constant k  2 did not change significantly. Similar changes were found for all evaluated scan durations. K  1 did not depend on scan duration (10 min- K  1 = 0.2191 vs 91 min- K  1 = 0.2258), while V  T and k  2 did. A scan duration of 10 min seems sufficient to properly evaluate the P-gp function using K  1 obtained with 1-TCM. For the 91-min scan, V  T and K  1 can be estimated with a 2-TCM, and both parameters can be used to assess P-gp function.

molecular pharmaceutics

Pharmacokinetic Modeling of [<sup>18</sup>F]MC225 for Quantification of the P-Glycoprotein Function at the Blood–Brain Barrier in Non-Human Primates with PET

Pharmacokinetic Modeling of [18F]MC225 for Quantification of the P-Glycoprotein Function at the Blood–Brain Barrier in Non-Human Primates with PET

Pharmacokinetic Modeling of [¹⁸F]MC225 for Quantification of the P-Glycoprotein Function at the Blood–Brain Barrier in Non-Human Primates with PET