Relative toxicity of ⁴⁵Ca β-particles and ²⁴²Cm α-particles following their intravenous injection into mice as radiolabelled FAP

Abstract

Purpose: To determine the relative toxicity of α- and β-radiations under conditions of controlled temporal and spatial dose distribution.

Methods: Fused aluminosilicate particles were radiolabelled with either ⁴⁵Ca (a β-emitter) or ²⁴²Cm (an α-emitter). These were injected into CBA/Ca mice to give lifespan, whole-body doses of ∼0.5, 1.0 or 1.5 Gy. Most animals were entered into a lifespan toxicity study, but some were killed for radiochemical analysis and autoradiography.

Results: Twenty-seven tumour types were identified. The most common malignant tumours were: Mammary carcinoma; liver carcinoma; malignant lymphoma; uterine histiocytic sarcoma. Excess relative risk (strictly hazard ratio) was higher for radiation-induced carcinomas than for sarcomas. The carcinomas, but not sarcomas showed a reduction in relative risk at the highest radiation dose employed. This reduction was most easily attributed to a systemic effect. The highest relative toxicity measured was for liver carcinoma (5.9, 95% confidence intervals [CI] 2.4, 14) and the lowest for uterine carcinoma (0.6, CI 0.03, 9.7). Overall, the excess relative risk ratio for survival was 1.9 (CI 1.1, 3.2), for all carcinoma was 2.3 (CI 1.7, 3.0) and for all sarcoma was 2.7 (CI 0.72, 10).

Conclusions: The 10-fold variability in the observed toxicity ratio for different tumour endpoints shows that tissue sensitivity is a more important determinant of relative toxicity than radiation quality. The use of single radiation-weighting (w_R) factors for radiation risk prediction and for radiological protection dosimetry is inconsistent with scientific observation.

Keywords:

• alpha emitters
• bystander effects
• carcinogenesis
• risk assessment
• histopathology
• RBE

Acknowledgements

Support in the USA was provided by research grants from the Department of Energy (DE-FC-09-02CH11109) and NASA (NAG9-1518). In the UK, both the original study and the UK contribution to this analysis of results were funded by the Department of Health. The authors acknowledge the following persons at the Harwell Laboratory who were either responsible for the day-to-day management of the programme or provided technical assistance: J. Kellington, C. Collier, T. Buckle, N. Timpson, M. Walsh, A. Black and P. Briden.

Declaration of interest: The authors have no conflicts of interest. They alone are responsible for the content and writing of the paper.