TY - JOUR
T1 - Improved Overall Survival of Mice by Reducing Lung Side Effects After High-Precision Heart Irradiation Using a Small Animal Radiation Research Platform
AU - Sievert, Wolfgang
AU - Stangl, Stefan
AU - Steiger, Katja
AU - Multhoff, Gabriele
N1 - Publisher Copyright:
© 2018 The Authors
PY - 2018/7/1
Y1 - 2018/7/1
N2 - 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 2 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 2 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.
AB - 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 2 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 2 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.
UR - http://www.scopus.com/inward/record.url?scp=85045561446&partnerID=8YFLogxK
U2 - 10.1016/j.ijrobp.2018.02.017
DO - 10.1016/j.ijrobp.2018.02.017
M3 - Article
C2 - 29680258
AN - SCOPUS:85045561446
SN - 0360-3016
VL - 101
SP - 671
EP - 679
JO - International Journal of Radiation Oncology Biology Physics
JF - International Journal of Radiation Oncology Biology Physics
IS - 3
ER -
