Radioimmunotherapy for Liver Micrometastases in Mice: Pharmacokinetics, Dose Estimation, and Long‐term Effect

The pharmacokinetics of a therapeutic dose of (131)I‐labeled antibody and the absorbed dose in liver micrometastases of human colon cancer LS174T in female BALB/c nu/nu mice were investigated, along with the long‐term therapeutic effect. Mice with liver micrometastases were given an intravenous injection of (131)I‐labeled anti‐carcinoembryonic antigen (CEA) antibody F33‐104 (8.88 MBq/40 μg). The biodistribution of the antibody was determined 1, 2, 4, 6, and 10 days later. The absorbed dose was estimated for three hypothetical tumor diameters; 1,000, 500, and 300 μm. Autoradiography showed a homogeneous distribution of radioactivity in the micrometastases, and a high uptake was maintained until day 6 (24.0 % injected dose (ID)/g on day 1 to 17.8 %ID/g on day 6), but decreased thereafter. The absorbed doses in the 1,000‐, 500‐, and 300‐μm tumors were calculated to be 19.1, 12.0, and 8.2 Gy, respectively. The intravenous injection of the (131)I‐labeled antibody also showed a dose‐dependent therapeutic effect (all mice of the nontreated group died, with a mean survival period of 4 weeks; 3 of the 8 mice that received 9.25 MBq survived up to 120 days with no sign of liver metastasis). These data give further evidence that micrometastasis is a good target of radioimmunotherapy, and that an absorbed dose of less than 20 Gy can effectively control small metastatic lesions.