RADIOBIOLOGY OF RADIOLABELED ANTIBODY THERAPY AS APPLIED TO TUMOR DOSIMETRY

This paper reviews the radiobiological aspects of radioimmunotherapy ( RIT) with radiolabeled antibodies, including comparisons between RIT a nd external beam irradiation. The effectiveness of cell killing by rad iation decreases with the dose rate and the rate of decrease is determ ined by the size of the shoulder on the radiation survival curve. Tumo rs with poor repair capabilities exhibit less of a dose rate effect th an tumors with good repair capabilities. Continued tumor cell prolifer ation during treatment occurs at very low dose rates and can contribut e to the reduced effectiveness of low dose rate radiation. Toxicity to normal tissues will determine the total dose of radiolabeled antibody that can be given and this will be influenced by the choice of both t he radionuclide and the antibody. The reported enhanced effectiveness of RIT may be due to multiple factors including selective targeting of cells responsible for tumor volume doubling, tumor surface binding ra ther than homogeneous binding throughout the tumor volume, targeting o f the tumor vasculature, or block of cell cycle progression in G2. Dur ing RIT, there is less time for reoxygenation of hypoxic tumor cells t han during a course of conventional external beam radiotherapy. It has not yet been determined whether this will have a detrimental effect o n RIT. Probably the most important factor in the success of RIT is dos e heterogeneity. Any viable portion of a tumor that is not targeted an d does not receive a significant radiation dose will potentially lead to treatment failure, no matter how high the dose received by the rema inder of the tumor. Comparisons between RIT and external beam radiatio n have shown a wide range of relative efficacy. Tumors most likely to respond to RIT are tumors with poor repair capabilities, tumors that a re susceptible to blockage in radiosensitive phases of the cell cycle, tumors that reoxygenate rapidly, and tumors that express the relevant antigen homogeneously. From a radiobiological perspective, it appears that RIT alone is unlikely to cure many tumors and that combination w ith other treatment modalities will be essential.