Preclinical models of radiation-induced lung damage: challenges and opportunities for small animal radiotherapy

Abstract

Despite a major paradigm shift in radiotherapy planning and delivery over the past three decades with continuing refinements, radiation-induced lung damage (RILD) remains a major dose limiting toxicity in patients receiving thoracic irradiations. Our current understanding of the biological processes involved in RILD which includes DNA damage, inflammation, senescence and fibrosis, is based on clinical observations and experimental studies in mouse models using conventional radiation exposures. Whilst these studies have provided vital information on the pulmonary radiation response, the current implementation of small animal irradiators is enabling refinements in the precision and accuracy of dose delivery to mice which can be applied to studies of RILD. This review presents the current landscape of preclinical studies in RILD using small animal irradiators and highlights the challenges and opportunities for the further development of this emerging technology in the study of normal tissue damage in the lung.

Figure 1.

Generalised schema of sequential inflammatory and fibrotic driven changes in the mouse lung following irradiation. Dependent on strain, mice may show some or all of these toxicities following exposure to ionising radiation. Based on Travis et al.

Figure 2.

A- Representative CBCT (coronal and axial section) with outlined target (healthy lung), organs at risk (oesophagus and heart) and isocentre. B- Representative dose volume histograms of the lungs, heart and oesophagus for a prescription dose of 20 Gy delivered using a small animal irradiator targeting a 30% sub volume of the lung (panel i); WTI (panel ii). The significant dosimetric advantage of small animal irradiators is highlighted with the critical OARs receiving minimal dose compared to WTI where the OARs receive most of the prescribed dose. CBCT, cone beam CT; OARs, organs at risk; WTI, whole thorax irradiation.