ESTRO 2024 - Abstract Book

S5246

Radiobiology - Normal tissue radiobiology

ESTRO 2024

3. Lamirault, C., et al., Short and long-term evaluation of the impact of proton minibeam radiation therapy on motor, emotional and cognitive functions. Sci Rep, 2020. 10(1): p. 13511.

4. Prezado, Y., et al., Tumor Control in RG2 Glioma-Bearing Rats: A Comparison Between Proton Minibeam Therapy and Standard Proton Therapy. Int J Radiat Oncol Biol Phys, 2019. 104(2): p. 266-271.

5. Bertho, A., et al., First Evaluation of Temporal and Spatial Fractionation in Proton Minibeam Radiation Therapy of Glioma-Bearing Rats. Cancers (Basel), 2021. 13(19).

789

Proffered Paper

Integrin antagonism to mitigate radiation-induced pulmonary fibrosis: iDISCO-based 3-D SHG imaging

William C Y Lo 1 , Peter G Ruminiski 2 , Amanda Klaas 1 , Felicia Grogan 1 , Lori Strong 1 , Julie K Schwarz 1 , Clifford G Robinison 1 , Buck E Rogers 1 , Carmen Bergom 1 1 Washington University School of Medicine, Radiation Oncology, St Louis, USA. 2 Washington University School of Medicine, Medical Oncology, St Louis, USA

Purpose/Objective:

Radiation-induced fibrosis is a dose-limiting normal tissue toxicity that significantly impacts the quality of life of patients undergoing radiation therapy and it is prevalent across numerous disease sites we treat in radiation oncology. In particular, radiation-induced pulmonary fibrosis (RIPF) is a potentially debilitating late complication from radiation therapy, especially in lung cancer patients with extensive disease burden and pediatric patients undergoing total body irradiation in preparation for stem cell transplantation. Unfortunately, RIPF has a poor prognosis with limited treatment options once it develops in patients. Integrins play a central role in the pathogenesis of RIPF, by serving as a major TGF-β activator after radiation injury, and are indeed implicated in fibrogenesis in numerous organs. The objective of this study is to investigate a small molecule RGD integrin inhibitor (both a preclinical compound and clinical analogue targeting αv integrins) to mitigate fibrosis development in a focal RIPF model. To evaluate the therapeutic response, whole organ fibrosis imaging was performed using iDISCO-based optical tissue clearing and second harmonic generation (SHG) imaging across the entire optically cleared lungs in 3-D at high-resolution.

Material/Methods:

Using XStrahl SARRP, we investigated the focal RIPF model (70 Gy delivered to a focal spot of 3 mm in the left lung, AP:PA configuration) using female C57BL/6J mice. The small molecule RGD integrin antagonists, preclinical compound CWHM-12 (targeting αvβ1, αvβ3, αvβ6, αvβ8) and clinical analogue (targeting αvβ1, αvβ3, and αvβ6), were administered at 50 mg/kg/day from weeks 4-8 post-RT, during the period of increased αv integrin expression as demonstrated in our prior work, in the focal RIPF model using the Alzet osmotic minipump. Tissue clearing was performed using the iDISCO protocol and 3-D whole organ fibrosis imaging was performed using SHG imaging for collagen quantification.

Results: