Improved Overall Survival of Mice by Reducing Lung Side Effects After High-Precision Heart Irradiation Using a Small Animal Radiation Research Platform.

PURPOSE

The aim was to reduce radiation exposure of the lung in experimental models to increase overall survival of mice to study late radiation-induced heart disease.

METHODS AND MATERIALS

A new irradiation plan was established on the Small Animal Radiation Research Platform machine for local heart irradiation of mice with single doses of 8 and 16 Gy. Lung damage was analyzed 20, 30, 40, and 50 weeks after irradiation by computed tomography scans and histology and compared with a sham-irradiated, age-matched, control group.

RESULTS

The use of an 8 × 6-mm collimator enabled local heart irradiation whereby only 18% of the lung received any irradiation. The V10 and V16 of the lung were 14% and 7%, respectively. After a mean heart dose of 8 and 16 Gy, mice survived for at least 50 weeks after irradiation. Computed tomography images demonstrated increased cell densities in the irradiated lung volume 50 weeks after irradiation. Concomitantly, histologic examination revealed fibrotic and inflammatory changes in the irradiated lung volume. In the heart, amyloid depositions and left ventricle hypertrophy were observed.

CONCLUSIONS

High-precision heart irradiation with 8 and 16 Gy using an 8 × 6-mm beam induced cardiac amyloidosis and hypertrophy, which did not lead to myocardial dysfunction despite the presence of radiation pneumopathy in the small V16 of the exposed lung. By using the improved irradiation plan (V16: 7%), long-term survival of the mice after heart irradiation can be achieved that allows clinically relevant experimental investigation of late radiation-induced heart disease effects.