Long-term imaging effects in rat liver after a single injection of an iron oxide nanoparticle based MR contrast agent

Purpose: To investigate the duration of liver R2* enhancement and pharmacokinetics following administration of an iron oxide nanoparticle in a rat model. Materials and Methods: Rats were injected with 0, 1, 2, or 5 mg Fe/kg of NC 100150 Injection, and quantitative in vivo 1/T2* liver measurements were obtained between I and 133 days after injection. The concentration of NC100150 Injection was determined by relaxometry methods in ex vivo rat liver homogenate. Results: At all dose levels, 1/T2* remained greater than control values up to 63 days after injection. In the highest dose group, 1/T2* was above control levels during the entire 133 day time-course investigated. There were no quantifiable amounts of NC 100 150 Injection present 63 days after injection in any of the dose groups. The half-life of NC100150 Injection in rat liver was dose dependent. For the lowest dose group, the degradation of the particles could be defined by a mono-exponential function with a half-life of eight days. For the 2 and 5 mg Fe/kg dose groups, the degradation was bi-exponential with a fast initial decay of seven to eight days followed by a slow terminal decay of 43-46 days. Conclusion: NC100150 Injection exhibits prolonged 1/T2* enhancement in rat liver. The liver enhancement persisted at time points when the concentration of iron oxide particles present in the liver was below method detection limits. The prolonged 1/T2* enhancement is likely a result of the particle breakdown products and the induction of ferritin and hemosiderin with increasing iron cores/loading factors.