A model of cell inactivation by alpha-particle internal emitters

Tumor-associated antibodies labeled with 131I and 90Y have been used in the treatment of malignant disease with some success. The use of alpha-particle-emitting radionuclides as radiolabels offers potential advantages over beta-particle sources. The short range in tissue (< 100 microns) and the high linear energy transfer associated with alpha-particle emitters will result in a more concentrated deposition of energy at the site of radionuclide decay. Thus, if radiolabeled antibodies can be bound to malignant cells specifically, a high differential cell killing can be achieved between the malignant and the normal cells. However, the energy deposition pattern will be strongly dependent upon the configuration of alpha-particle sources relative to the cells, and will consequently impact upon the dose-response characteristics. The purpose of this paper is to study distributions of energy deposition from alpha-particle-emitting radioimmunoconjugates distributed uniformly and nonuniformly around cells through theoretical modeling. Energy deposition spectra for cell nuclei are calculated and used to estimate the survival fraction by a simple biological model. We show that survival curves resulting from nonuniform distributions of alpha-particle-emitting radiolabeled antibodies can depart significantly from the classical exponential survival model applied to external alpha-particle beams. The survival curves may have initial slopes much steeper than those produced by a uniform distribution of sources, and they may also depart from linearity. Furthermore, the results of the modelling indicate how survival curves are dependent on the cell and radiolabel spacing. The results from our model compare reasonably well with published experimental data and can be used to facilitate the design and interpretation of radiobiological experiments.