Whole body [O-15]water pharmacokinetics measured in blood

A simple pharmacokinetic model to explain the time course of [O-15]water in human whole blood after bolus injection is described. The model has been derived from measurements in twelve healthy volunteers who were measured repeatedly, resulting in 67 datasets, made in the context of PET blood flow studies. In contrast to traditional volume of distribution estimates of total body water (TBW) which rely on measurements after many hours, the model and data provide insights into the fast uptake components in the distribution of water in the body. Data fitting shows that the volume of distribution of fast exchanging tissues is 21 l, TBW was calculated to be 37 l. Monte Carlo simulation showed that the expected inaccuracy of determination of parameters due to unsystematic sources in the measurement data was around 5% for most parameters. Our data show that water extraction to tissue is somewhat higher than would be predicted from the tabulated values, probably because skeletal blood flow is sensitive to physiological status and environmental conditions. The study provides valuable reference data on the distribution and kinetics of water in man. Using the parameters and model from this study, reference input time-activity curves can be calculated, e.g. for the Monte Carlo study of error propagation in PET studies.