Hepatocyte-specific contrast media for CT. An experimental investigation.

Abstract

CT is an important technique in liver imaging. To improve the detection of focal liver lesions the use of non-specific, water-soluble contrast media (CM) is mandatory. However, even with use of these CM the sensitivity in tumour detection is low. In the development of liver-specific CM, the majority of the agents have been targeted to the reticuloendothelial system (RES). The clinical use of RES-specific contrast agents has been hampered by frequent adverse reactions, and a new concept whereby the CM is taken up by the hepatocytes has been developed as an alternative. Such a CM is taken up by normal liver parenchyma but not by tumour cells, enhancing the difference between normal and pathological tissue, and therefore improving the diagnostic sensitivity. In the present investigation, FP 736-03 and FP 736-04, two hepatocyte-specific lipid emulsions, have been studied using animal models. In normal liver parenchyma dose-dependent enhancement was found, whereas in tumour tissue of experimental liver metastases and hepatocellular carcinoma, no enhancement was noted. The virtually unchanged attenuation in tumour tissue meant that the liver-to-lesion contrast increased steadily during the observation period. In an attempt to establish the relationship between enhancement and tumour detection, the accumulated doses of FP 736-04 were used. Increasing accuracy in the diagnosis of liver metastases was found up to an enhancement level of 30 HU. A further increase yielded similar detection rates, but a higher proportion of false-positive results. Comparison with iohexol was rendered difficult by the occurrence of image artefacts when this CM was used. However, FP 736-03 proved superior to both native and iohexol-enhanced CT for detection of hepatic metastases. The efficacy of FP 736-04 was also studied in diseased hepatic parenchyma. In cases of fatty liver infiltration, enhancement by FP 736-04 was significantly reduced as compared with normal controls. The degree of enhancement observed in cirrhotic livers did not differ significantly from that in the controls. These preclinical investigations have shown that the hepatocyte-specific lipid emulsions FP 736-03 and FP 736-04 improve the diagnostic accuracy of focal liver lesions as compared to native and water-soluble CM-enhanced CT. FP 736-04 is taken up by diseased liver parenchyma. However, the detection of malignancy in steatotic and cirrhotic livers has not yet been studied with use of this CM.