Optimum combination of targeted¹³¹I therapy and total-body irradiation for treatment of disseminated tumors of differing radiosensitivity

Abstract

¹³¹I is the radionuclide most commonly used in biologically targeted radiotherapy at the present time. Microdosimetric analysis has shown that microtumors whose diameters are less than the β-particle maximum range absorb radiation energy inefficiently from targeted radionuclides. Micrometastases of diameters <1 mm are likely to be spared if targeted¹³¹I is used as a single modality. Because of this, combined modality therapy incorporating targeted¹³¹I, external beam total-body irradiation (TBI), and bone marrow rescue has been proposed. In this study, the minimum necessary TBI component is shown to depend on the radiosensitivity of the tumor cells. The analysis shows that the TBI component, to achieve radiocurability, increases directly with tumor radioresistance. For the most radiosensitive tumors, a whole-body TBI treatment dose 2×2 Gy is calculated to be obligatory, whereas practical tumors, the analysis implies that a TBI treatment delivery of 5×2 Gy is obligatory. In all situation, external beam TBI appears to be an essential factor in providing reasonable probability of cure of disseminated malignant disease. Reasonable prospects of tumor cure by combination strategies incorporating¹³¹I exist for the more radiosensitive tumor types (e.g., neuroblastoma, lymphoma, leukemia, myeloma, seminoma), but more resistant tumors are unlikely to be curable at present. Superior targeting agents, and the possible use of panels of different radionuclides, may be necessary to achieve high cure probabilities for less radiosensitive tumor types.