Micro-CT Imaging with a Hepatocyte-selective Contrast Agent for Detecting Liver Metastasis in Living Mice

Abstract

Micro-computed tomography (CT) is a important tool for longitudinal imaging of tumor development. The detection and monitoring of tumors in the liver in live animals using micro-CT is challenging. We evaluated the feasibility of high-resolution micro-CT enhanced with a hepatocyte-selective contrast agent for detecting liver metastases in a live murine model. Hepatic metastases were induced in 10 BALB/C mice. Two mice each were randomly selected on days 3, 5, 7, 10, and 13 after CT26 colon adenocarcinoma cells were injected into the portal vein; micro-CT imaging was performed at 10 minutes and 4 hours after intravenous administration of a hepatocyte-selective contrast agent at a dose of 0.4 mL/mouse. The attenuation values of the normal liver and the tumors were obtained. The number of metastases was counted and their sizes were measured on the micro-CT images. Gross or histopathologic evaluation was performed for correlating the liver tumors with the micro-CT images. A total of 74 separate tumor sites larger than 300 microm in diameter were detected on pathologic examination of the mice that were sacrificed 7 days after cell injection. On micro-CT, 66 of 74 tumors were detected (83.8%). The smallest tumor detected on micro-CT was 300 microm. There were eight false-negative readings on micro-CT. The sizes of the individual liver metastases measured by micro-CT and on the excised specimen were highly correlated (P < .001). The correlation between the CT scan measurement and the actual measurement was r = 0.8354 (P < .0001). High-resolution micro-CT enhanced with a hepatocyte-selective contrast agent can be a promising tool for detecting liver metastases in a live murine model.