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Pharmacokinetic modeling of phagocytic activity of the liver using superparamagnetic iron oxide nanoparticles in
Jae Boem Na1, Jin-Suck Suh, Yong-Min Huh
1Department of Diagnostic Radiology, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752, Korea.
Abstract:
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 Tc99m-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 maximum 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.
Insights
Dynamic MRI using superparamagnetic iron oxide (AMI-25) can quantify phagocytic activity. The ratio of distribution volumes (Rv) effectively indicates reduced liver phagocytic function in animal models.
Area of Science:
- Medical Imaging
- Biophysics
- Pharmacology
Background:
- Phagocytic activity is crucial for liver function.
- Measuring phagocytic activity non-invasively is challenging.
- Superparamagnetic iron oxide nanoparticles offer potential for MRI contrast.
Purpose of the Study:
- To assess if dynamic superparamagnetic iron oxide-enhanced MRI can measure phagocytic activity.
- To evaluate the ratio of distribution volumes (Rv) as an index of phagocytic function.
- To investigate the effect of silica treatment on phagocytic activity using MRI.
Main Methods:
- Dynamic MRI studies were performed on New Zealand White rabbits and Beagle dogs.
- Superparamagnetic iron oxide (AMI-25) was administered, and data from the kidney and liver were analyzed.
- A three-compartment model was applied to calculate the ratio of distribution volumes (Rv).
- Radioisotope studies with Tc99m-phytate were used for comparison.
Main Results:
- The ratio of distribution volumes (Rv) reached maximum values around 80 minutes post-injection.
- The Rv in the normal rabbit group was 5.06 +/- 1.53, significantly higher than the silica-treated group (2.13 +/- 1.20).
- Results correlated with radioisotope study data, showing decreased Rv with silica treatment.
- Rv was independent of the injected dose of AMI-25.
Conclusions:
- Dynamic superparamagnetic iron oxide-enhanced MRI can quantitatively assess phagocytic activity.
- The Rv value serves as a reliable index for decreased liver phagocytic activity.
- This MRI technique offers a non-invasive method for evaluating liver function related to phagocytosis.
