Kopp-Schneider, A., Haertel, T., Burkholder, I., Bannasch, P., Wesch, H., Groos, J. and Heeger, S. Investigating the Formation and Growth of α-Particle Radiation-Induced Foci of Altered Hepatocytes: A Model-Based Approach. Radiat. Res. 166, 422–430 (2006).
The effect of α-particle radiation on the formation and increase in volume of preneoplastic liver lesions was investigated in an animal experiment. Mice were divided into four groups; two groups received different doses of the α-particle-labeled antibody 213Bi-anti CD19 (213Bi-CD19), Thorotrast was administered to one group, and one group was left untreated. Hematoxylin and eosin-stained liver sections were evaluated for preneoplastic foci of altered hepatocytes 6, 12 and 17 months after treatment. The density and size distribution of focal transections were described by a mechanistic model for the formation and growth of foci of altered hepatocytes. The negative control and the 213Bi-CD19 groups were combined to investigate the dose–response relationship for model parameters describing the formation and growth of foci of altered hepatocytes. Although 213Bi-CD19 was given by single injection, the effect on formation of foci of altered hepatocytes lasted for the entire experiment. Likelihood-ratio tests comparing nested models showed that 213Bi-CD19 increases the rates of both the formation and growth of foci of altered hepatocytes. Comparing the effects of Thorotrast with those of 213Bi-CD19 revealed that Thorotrast had an effect similar to that of a low dose of 213Bi-CD19, but the effect on focus formation was slightly smaller whereas the effect on focus growth was slightly higher for Thorotrast, in contrast to a low dose of 213Bi-CD19.