Uptake of long-circulating immunoliposomes, directed against colon adenocarcinoma cells, by liver metastases of colon cancer

Radiolabeled ([H-3]cholesteryloleyl ether) immunoliposomes directed against rat colon adenocarcinoma CC531 cells were prepared by random coupling of a tumor cell-specific antibody, CC52, via a thio-ether bond. In vitro bindin g experiments demonstrated a saturable and specific interaction of CC52-imm unoliposomes, which could be inhibited by free non-coupled CC52 but not by irrelevant antibodies. The in vivo targeting potential of CC52-immunoliposo mes, which were pegylated to achieve prolonged circulation times, was teste d in an established rat liver CC531 metastasis model. Twenty-four hours aft er injection of the liposomes, 25% of the CC52-immunoliposomes were still p resent in the blood, which was comparable with the control liposomes (eithe r with or without antibody). Liposomes were mainly taken up from the blood by the liver and the spleen, although hepatic uptake of the immunoliposomes was higher and splenic uptake was lower as compared to liposomes without a ntibody. Within the metastatic tumor nodules in the liver, uptake of both t he CC52-immunoliposomes and non-specific immunoliposomes was significantly higher than that of control liposomes without antibody. Visualization of fl uorescently or gold labeled CC52-immunoliposomes revealed that, although ta rgeting to liver metastases was achieved, the immunoliposomes were mostly n ot associated with tumor cells but rather localized in tumor associated cel ls, probably macrophages.