Quantification of Dynamic ¹¹C-Phenytoin PET Studies

Abstract

The overexpression of P-glycoprotein (Pgp) is thought to be an important mechanism of pharmacoresistance in epilepsy. Recently, ¹¹C-phenytoin has been evaluated preclinically as a tracer for Pgp. The aim of the present study was to assess the optimal plasma kinetic model for quantification of ¹¹C-phenytoin studies in humans. Methods: Dynamic ¹¹C-phenytoin PET scans of 6 healthy volunteers with arterial sampling were acquired twice on the same day and analyzed using single- and 2-tissue-compartment models with and without a blood volume parameter. Global and regional test–retest (TRT) variability was determined for both plasma to tissue rate constant (K₁) and volume of distribution (V_T). Results: According to the Akaike information criterion, the reversible single-tissue-compartment model with blood volume parameter was the preferred plasma input model. Mean TRT variability ranged from 1.5% to 16.9% for K₁ and from 0.5% to 5.8% for V_T. Larger volumes of interest showed better repeatabilities than smaller regions. A 45-min scan provided essentially the same K₁ and V_T values as a 60-min scan. Conclusion: A reversible single-tissue-compartment model with blood volume seems to be a good candidate model for quantification of dynamic ¹¹C-phenytoin studies. Scan duration may be reduced to 45 min without notable loss of accuracy and precision of both K₁ and V_T, although this still needs to be confirmed under pathologic conditions.