131-iodine conjugated antibody cell kill enhanced by bromodeoxyuridine.
131I-conjugated monoclonal and polyclonal antibodies are being administered in vivo to kill human tumor cells. Although these conjugates deliver relatively large doses of radiation to tumors (10 to 50 Gy), the rate of dose delivery is low (0.05 to 0.2 Gy/hour). Radiation delivered at low dose rates kills fewer cells that exhibit large shoulders on radiation survival curves than radiation delivered at high dose rates. To determine whether the cell kill produced by low dose rate radiation is enhanced by a radiation sensitizer (bromodeoxyuridine, BUdR) we studied the cell kill produced by an 131I-conjugated polyclonal antibody against Chinese hamster V79 cells. V79 cells were labeled with 131I-conjugated antibody (10-20 microCi/micrograms) and unconjugated antibody, and frozen for up to 30 days in liquid nitrogen. The surviving fraction of cells was measured at intervals of 5 to 10 days. Cells not containing BUdR were also studied. The 131I-conjugated antibody produced up to 40% cell kill and BUdR increased the fraction of cells killed to 75%. Our studies demonstrate that cells frozen at -196 degrees C are useful for the investigation of the cell kill produced by isotopes that deliver radiation at low dose rates and that the cell kill caused by 131I-conjugated antibodies can be enhanced by BUdR.
D000818:Animals; D000906:Antibodies; D001973:Bromodeoxyuridine / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D006224:Cricetinae; D003412:Cricetulus; D005615:Freezing; D007457:Iodine Radioisotopes; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D013997:Time Factors
D000906:Antibodies; D007457:Iodine Radioisotopes; D011838:Radiation-Sensitizing Agents; D001973:Bromodeoxyuridine