ESTRO 2024 - Abstract Book

S5247 ESTRO 2024 Integrin antagonism with both preclinical and clinical small molecule RGD inhibitors from weeks 4 to 8, during the window of increased αv integrin expression, significantly attenuated fibrosis development in the focal RIPF model, as quantified by 3D SHG imaging in optically cleared lungs (Fig. 1). The volume of the fibrotic region, assessed using SHG imaging, was significantly reduced from 4.09 +/- 0.75 mm 3 in the sham-treated/control group to 1.56 +/- 0.23 mm 3 (P=0.035) in the group treated with the preclinical compound CWHM-12 and 1.43 +/- 0.27 mm 3 (P=0.029) in the group treated with our clinical analogue, at 8 weeks post-RT (Fig. 2). Radiobiology - Normal tissue radiobiology

Conclusion:

Integrin antagonism, targeted during the period of increased αv integrin expression, significantly attenuated fibrosis development in the focal RIPF model using iDISCO-based optical clearing and quantification with volumetric SHG imaging across the optically-cleared whole lungs. The whole organ tissue clearing and SHG imaging framework is widely applicable for quantification of collagen and assessment of fibrosis at high-resolution in 3-D in a variety of organs, providing a powerful tool for the evaluation of therapeutic response to novel antifibrotic therapeutics, as demonstrated here. Furthermore, given the central role αv integrins play in fibrogenesis across a variety of organs, this study has significant implications for the mitigation of radiation induced fibrosis, which is an important dose-limiting side effect in radiation therapy.