Kinetic modeling of benzodiazepine receptor binding with PET and high specific activity [C-11]Iomazenil in healthy human subjects

Quantitation of the PET benzodiazepine receptor antagonist, [C-11]Iomazenil , using low specific activity radioligand was recently described. The purpo se of this study was to quantitate benzodiazepine receptor binding in human subjects using PET and high specific activity [C-11]Iomazenil. Six healthy human subjects underwent PET imaging following a bolus injection of high s pecific activity (>100 Ci/mmol) [C-11]iomazenil. Arterial samples were coll ected at multiple time points after injection for measurement of unmetaboli zed total and nonprotein-bound parent compound in plasma. Time activity cur ves of radioligand concentration in brain and plasma were analyzed using tw o and three compartment model. Kinetic rate constants of transfer of radiol igand between plasma, nonspecifically bound brain tissue, and specifically bound brain tissue compartments were fitted to the model. Values for fitted kinetic rate constants were used in the calculation of measures of benzodi azepine receptor binding, including binding potential (the ratio of recepto r density to affinity), and product of BP and the fraction of free nonprote in-bound parent compound (V-3'). Use of the three compartment model improve d the goodness of fit in comparison to the two compartment model. Values fo r kinetic rate constants and measures. of benzodiazepine receptor binding, including BP and V-3', were similar to results obtained with the SPECT radi oligand [I-123]iomazenil, and a prior report with low specific activity [C- 11]Iomazenil. Kinetic modeling using the three compartment model with PET a nd high specific activity [C-11]Iomazenil provides a reliable measure of be nzodiazepine receptor binding. Synapse 35:68-77, 2000. Published 2000 Wiley -Liss, Inc.dagger