Long-term survival and toxicity in Balb/c mice after systemic administration of alpha emitters

NUCL 85

Horst Wesch1, Steffen Heeger2, Frauke Spiecker1, Folker Amelung1, Martin W. Brechbiel3, Gerhard Moldenhauer2, and Tuomo Nikula4. (1) Department of Radiology, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany, (2) Department of Molecular Immunology, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany, (3) NCI, NIH, Building 10, Room B3B69, 10 Center Drive, Bethesda, MD 20892-1002, (4) European Institute for Transuranium Elements, Karlsruhe, Germany
In recent years radioimmunotherapy (RIT) with beta- or alpha-particles emitting radionuclides has been used in experimental and clinical settings for cancer therapy. To assess possible late effects of the novel therapeutic modality together with the comparison of acute versus chronic alpha radiation a long-term animal experiment was performed. Two groups were injected intravenously with a short-lived Bi-213-labeled antibody (4.7 MBq/animal and 1 MBq/animal), one with a long-lived alpha-emitter (Th-232 dioxide) and one untreated group. Dose dependent reduction in survival was observed in all groups receiving the treatment. Significant morphological differences compared to the controls were seen in the liver, spleen, lungs, heart and the adrenal glands in the 4.7 MBq group. Furthermore, in this group the formation of thrombi in the aorta was observed causing embolic damages. All these effects occurred more than one year after treatment. Future experiments should clarify whether these observations are radiation or mouse strain specific.