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Pharmacokinetics of superparamagnetic iron-oxide MR contrast agents in the rat
S Majumdar1, S S Zoghbi, J C Gore
1Department of Radiology, Yale University, New Haven, Connecticut.
Abstract:
The in vivo pharmacokinetics and the biodistribution of superparamagnetic iron-oxide particles (AMI25, Advanced Magnetics, Cambridge, MA) were investigated in anesthetized rats. Four different dose concentrations, ranging from 49.8 to 408.9 mumol of Fe (or 2.78-22.84 mg Fe) per kilogram, radiolabeled with 6.0 microCi of 59Fe-AMI25 were injected intravenously into 18 rats. The radioactivity cleared from the circulation with a fast component with a half-life of approximately 10 minutes and a slower component with a half-life of 92 minutes. Both half-lives were independent of the injected dose (ID) in the range of 105.4-408.9 mumol (5.89-22.84 mg) Fe/kg. The relative uptake in the liver, spleen, and kidneys was 57%, 2.9%, and 2.0% of the ID, respectively. At a dose of 52.1 mumol (2.91 mg) of Fe/kg, the relative concentration of iron significantly increased in the liver and decreased in the blood. Within the kidney, autoradiography showed that the iron was selectively taken up by the cortex. In the kidney, a concentration of 0.23 mumol (0.013 mg) Fe/g resulted in a 30% reduction in image intensity in a single echo magnetic resonance image obtained using a spin-echo sequence and an echo time of 70 ms.
Insights
Superparamagnetic iron-oxide particles (AMI25) show rapid clearance from rat circulation. Liver and spleen accumulate the highest iron concentrations, with selective uptake in the kidney cortex, impacting MRI signal intensity.
Area of Science:
- Biomedical Engineering
- Radiopharmacology
- Nanotechnology
Background:
- Superparamagnetic iron-oxide particles (SPIOs) are utilized as contrast agents in Magnetic Resonance Imaging (MRI).
- Understanding the in vivo behavior of SPIOs is crucial for optimizing their diagnostic applications.
Purpose of the Study:
- To investigate the pharmacokinetics and biodistribution of AMI25, a specific SPIO formulation, in an in vivo rat model.
- To assess the dose-dependency of AMI25's clearance and tissue accumulation.
- To evaluate the impact of iron concentration in the kidney on MRI signal intensity.
Main Methods:
- Intravenous injection of 59Fe-radiolabeled AMI25 into anesthetized rats at various dose concentrations.
- Measurement of radioactivity in circulation over time to determine pharmacokinetic parameters (half-lives).
- Quantification of iron uptake in major organs (liver, spleen, kidneys) and autoradiography for kidney cortex localization.
- Assessment of MRI signal changes in the kidney cortex following iron administration.
Main Results:
- AMI25 exhibited biphasic clearance from circulation with half-lives of approximately 10 and 92 minutes, independent of dose within the tested range.
- The liver showed the highest relative uptake (57%), followed by the spleen (2.9%) and kidneys (2.0%).
- A significant increase in liver iron concentration and a decrease in blood iron were observed at a specific dose, with selective iron uptake in the renal cortex.
Conclusions:
- AMI25 demonstrates predictable pharmacokinetics and biodistribution in rats, with preferential accumulation in the liver.
- The selective uptake of iron in the kidney cortex suggests potential for targeted MRI contrast enhancement.
- Kidney iron concentration directly correlates with reduced MRI signal intensity, indicating its utility as an MRI contrast agent in renal imaging.