Experimental radioimmunotherapy: biological effectiveness and comparison with external beam radiation.

Abstract

Wessels (1990; Wessels et al. 1989) proposed that in order to assist in the prediction of the clinical efficacy of radioimmunotherapy (RIT) a radiobiological characterization of a tumor in animals be performed by correlating animal model data of external beam radiation therapy (XRT) and data of RIT in the same model and then measuring the absorbed dose in each. The fundamental question is whether or not the overall effect of 1 cGY of RIT is equivalent to that of 1 cGy of XRT. The dose rate at which the two are delivered is different, XRT being delivered at a high dose rate while RIT irradiation is delivered at a low dose rate, usually at rates lower than with implant therapy. In addition, the dose rate is decreasing with time due to the physical decay and biological clearance of the radionuclide from tumor and normal tissues. Furthermore, there are many geometric and biological factors that affect the homogeneity of dose deposition from RIT. A similar comparison approach would be used to convert animal RIT data to clinical RIT trials as has been used to compare animal and clinical XRT data (Wessels 1990; Knox et al. 1992; Fowler 1990; Orton and Cohen 1988; Dale 1985). By deriving a ratio of radiobiological response for the same tumor cell line between RIT and XRT in animals, a predictive response ratio would be obtained when examining the potential efficacy of different radiolabeled monoclonal antibodies (MAbs) for clinical trials.