DETERMINANTS OF LOW-DOSE RATE EFFECTS ASSOCIATED WITH RADIOIMMUNOTHERAPY

The murine B cell lymphoma 38C13 model was used to study components of low dose rate (LDR) irradiation that may be important to the overall efficacy of radioimmunotherapy (RIT). Initially groups of mice were tr eated with equivalent total doses at different dose rates for either 4 0 or 80 hours. The higher dose rate, had a greater anti-tumor effect w hich reached statistical significance (p=0.001) only when cumulative e ffects were compared. In subsequent experiments, mice were treated wit h similar whole body doses of either a) contintuous exponentially decr easing (ED) Cs-137 gamma-irradiation which simulated the effective t1/ 2 of I-131-anti-idiotypic monoclonal antibody over 10 days, b) continu ous constant gamma-irradiation given for 10 days (C-LDR), c) continuou s constant gamma-irradiation at a dose rate equal to the initial dose rate of the ED group for the period of time required at that dose rate to deliver the desired equivalent total dose (C-DR(o)), or d) multifr actionated (MF) 250 kV X-irradiation given in 10 equal daily fractions . Within experiments, the effect of these modes of irradiation on tumo r size differed significantly. In general, the relative efficacy of th e different modes of dose equivalent irradiation can be ranked as foll ows: ED > MF = C-DR(o) > C-LDR. These results suggest that the increas ed efficacy of ED compared with equivalent doses of the other modes of irradiation may be due in part to the deposition of a large proportio n of the total dose early in the irradiation period, with an initial d ose rate in the range achievable with RIT (e.g. 15-30 cGy/hr), followe d by continued decaying LDR irradiation. Thus in the 38C13 B cell muri ne lymphoma model, important determinants of the overall effect of LDR irradiation associated with RIT am a) total dose, b) dose rate and ma ximal dose rate, c) length of time of irradiation and d) mode of irrad iation (e.g. ED).