Biodistribution of radiolabeled monoclonal antibody after intraperitoneal administration in nude mice with hepatic metastasis from human colon cancer

Abstract

The utility of the intraperitoneal (IP) administration of radiolabeled monoclonal antibody (mAb) for hepatic metastasis from human colon cancer was evaluated in congenital athymic mice. The intrasplenic injection of HT-29 LMM metastatic human colon cancer cell line reproducibly results in hepatic metastasis formation in nude mice. HT-29-15, a murine mAb of IgG1 class reactive with the HT-29 LMM cell line was labeled with iodine 125. One μg/2 μCi of labeled HT-29-15 was injected intraperitoneally into mice with hepatic metastases, and additionally IP administration of the same dose of I-125 labeled HT-29-15 with increased volume and intravenous (IV) administration of dose quantity of HT-29-15 were performed. Blood samples were obtained at 1, 3, 5 hours, and the animals were sacrificed on days 1, 3, and 5. The per cent of injected dose per gram (%ID/g) of blood after IP administration of I-125 labeled HT-29-15 reached the same level of %ID/g after IV administration by 5 hours. The transfer from the peritoneal cavity to blood was delayed by increasing the volume injected. From day 1 to day 3, there was a progressive increase for hepatic metastasis/blood ratios of I-125 labeled HT-29-15 in each group. There was no difference in the hepatic metastasis/blood ratios among the three groups. IP administration of specific mAb, therefore, provides the same level of tumor uptake in hepatic metastasis from colorectal cancer, and would be advantageous in patients with both hepatic metastasis and peritoneal implants in which radioimmunodetection and radioimmunotherapy are appropriate.