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

摘要

The pharmacokinetics of a therapeutic dose of ¹³¹I‐labeled antibody and the absorbed dose in liver micrometastases of human colon cancer LS174T in female BALB/c nuu mice were investigated, along with the long‐term therapeutic effect. Mice with liver micrometastases were given an intravenous injection of ¹³¹I‐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 ¹³¹I‐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.