Superparamagnetic iron oxide nanoparticles as a dual imaging probe for targeting hepatocytes in vivo

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Abstract
Hepatocyte‐specific targeting agents are useful for evaluation of the hepatocytic function and the monitoring of disease progress. Superparamagnetic iron oxide nanoparticles (SPION) bearing terminal galactose groups exhibit a high affinity for the asialoglycoprotein receptor on the hepatocyte surface. In this study, we synthesized and characterized the dual probe SPION detectable by both nuclear and MR imaging modality for specifically targeting hepatocytes in vivo. SPION with 12‐nm diameter were functionalized with dopamine. Surface modification of the SPION was performed to target asialoglycoprotein receptor on hepatocytes, using lactobionic acid. Transmission electron microscope images demonstrated that SPION displayed highly uniform characteristics in terms of both particle size and shape. The X‐ray diffraction pattern of SPION revealed a nanocrystal structure of magnetite. To radiolabel the magnetite with 99mTc, diethylenetriaminepentaacetic acid was conjugated to unreacted functional groups of dopamine. 99mTc‐labeled lactobionic acid‐SPION showed high accumulation in liver, with 38.43 ± 6.45% injected dose per gram. In MR imaging, the reduction of the T2 signal in the liver by lactobionic acid‐SPION was approximately 50.8 ± 7.3%. Competition studies and transmission electron microscope images of liver tissues demonstrated that the lactobionic acid‐SPION were localized in hepatocytes. Therefore, the lactobionic acid‐SPION may be used as a hepatocyte‐targeted dual contrast agent for both nuclear and MR imaging. Magn Reson Med, 2009.

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