ESTRO 2024 - Abstract Book

S5233

Radiobiology - Normal tissue radiobiology

ESTRO 2024

45

Digital Poster

Optimal dose and volume inducing radiation pulmonary fibrosis in a preclinical small animal model

Ronglan Cui, Jae Hee Lee, Sang Yoen Kim, Sunjoo Park, Hyo Jeong Song, Hai In Jo, Farh Moharmed El-Agamy, jaeho Cho

Yonsei University College of Medicine, Department of Radiation Oncology, Seoul, Korea, Republic of

Purpose/Objective:

For many decades, radiation therapy plays an important role in multidisciplinary treatment of thoracic malignancy. Radiation therapy is an increasingly significant treatment for lung cancer patients, and one of its most common and fatal adverse effects is radiation induced pneumonitis and fibrosis. In clinical settings, it takes more than six months for radiation induced pulmonary fibrosis to occur after treatment with high-dose radiation. In animal models, the onset time of radiation induced lung fibrosis need to be shortened to within two months due to experimental limitations. With the continuous emergence of novel anti-fibrotic drugs, the aim of this study is to establish a preclinical model of radiation induced lung fibrosis that is suitable for evaluation of anti-fibrotic drugs.

Material/Methods:

7-week-old male C56BL/6 mice were given a single high dose of irradiation on the left lung using X-RAD 320 biological irradiator. The percentage depth doses(PDD) were obtained using a cylindrical ionization chamber within a solid water phantom (PTS, RW3) at a source-to-surface distance of 170mm. The radiation dose given to the mice was a relative value due to the curvature of the mouse lung surface as a result of the PDD measurement. We selected dose levels of 45Gy, 55Gy, 65Gy, 75Gy and 85Gy were delivered through 4mm and 5mm collimators to groups of five mice, totaling fifty mice. Micro-CT, histopathological examination and bronchoalveolar lavage fluid analysis were used to evaluate different response to different doses and volume. Pulmonary function and blood serum immunoglobulin were additionally analyzed.

Results:

At the six-week time point, mice were observed for radiation induced lung fibrosis. As radiation dose level increased, micro-CT images of the lung showed significant increase in damaged area with 4mm and 5mm collimators, respectively. Given the same radiation dose of 75Gy, compared to only three out of five in the 4mm collimator group with lesions of radiation damage, all five mice in the 5mm group had lesions at the identical location examined histologically. Additionally, lung damage in the 85Gy group both with 4mm and 5mm collimators was excessively severe. Histopathologically, fibrosis correlated marker, α-SMA and fibronectin level were proportional to increases in radiation dose and volume. Changes in pulmonary function were corresponded to the radiation dose and volume. Infiltration of inflammatory cells, indicated by the number of lymphocytes in the bronchoalveolar lavage fluid collected at six weeks, increased most significantly with increasing radiation dose. The level of cytokine (IL-6, INF-γ, TGF-β, IL-1β, TNF-α, IL-4) in 5mm collimator group is lower than 4mm collimator group. Changes in immunoglobulin IgG isotype IgG1 and IgE showed increasingly higher until 75Gy but decreased at 85Gy.

Conclusion: