Pharmacokinetic modeling of phagocytic activity of the liver using superparamagnetic iron oxide nanoparticles in dynamic MR imaging

The purpose of this study was to determine whether phagocytic activity is measurable by dynamic superparamagnetic iron oxide-enhanced MR imaging. For these experiments on New Zealand White rabbits, which were randomly allocated to normal and silica treated groups, we performed a dynamic MR study and radioisotope study with Tc^99m-phytate. In this dynamic MR study, the ratio (Rv) of the distribution volumes of iron oxide (Vm/Ve) could be obtained by applying three-compartment model to the data obtained from the kidney and liver simultaneously. Changes in Rv caused by silica injection and by dosing superparamagnetic iron oxide, AMI-25, were evaluated. In the dynamic MR study using a Beagle dog model the input function could be calculated from data obtained from the hepatic artery and portal vein. Rv's reached maxinium values at around 80 minutes after the AMI-25 injection. The Rv of the normal group was 5.06 ± 1.53 whereas the Rv of the silica treated group was 2.13 ± 1.20. The results were similar to tissue count data obtained by radioisope study. The Rv value was not dependent on the injected dose of AMI-25. The rate of transport constants (k1, k2, k3) could not be estimated using the 3 compartment model regardless of obtaining the input function. We conclude that Rv may be an quantitative index of decreased phagocytic activity in the liver as determined by dynamic superparamagnetic iron oxide-enhanced MRI.