Abstract 1144: Imaging radiotherapy induced pulmonary fibrogenic changes with integrin-PET

Abstract

Abstract Integrin αvβ6 plays a key role in the fibrotic pathway by activation of Transforming Growth Factor β. Expression of αvβ6 integrin in alveolar epithelium increases after radiotherapy (RT) before onset of fibrosis and anti- αvβ6 therapy prevents fibrogenesis. Post-RT lung fibrosis, a major barrier to improved cure rate presents as progressive pulmonary injury. The utility of PET imaging with a αvβ6 integrin ligand was evaluated in patients with non-small cell lung cancer following pulmonary RT. Subjects who had received pulmonary RT within 6 months were recruited. PET imaging of the lungs over 60 minutes was performed after administration of a fluorine-18 radiolabelled 20 amino acid αvβ6-specific peptide ligand, [18F]-FBAA20FMDV2 (IMAFIB; Cancer Research Technologies (CRT) patented). PET-CT scans were co-registered with the RT planning (RTP) scans and segmented to regions corresponding to RT doses of > 40 Gy (excluding tumour), 25-40 Gy, 15-25 Gy, 8-15 Gy and < 8 Gy. Time activity curves and the standardised uptake values (SUVs) were calculated and comparisons made between RT dose and PET uptake (SUV). Linear regression between SUV and RT dose was performed for each subject and normalised to an intercept of 1. 6 subjects (3M; 3 F) aged 51-75 years underwent an IMAFIB-PET scan between 6 -22 weeks after RT completion and mean IMAFIB radioactivity of 45.4 (range 8.9 – 122) MBq administered. 5 subjects received conformal external beam RT, while one subject received stereotactic RT (SBRT). A correlation between a higher PET uptake (SUV) and higher RT doses received by the lung was observed in all subjects with a significant relationship (p < 0.05) in 3 of the 6 subjects (table). The averaged normalised SUV across all subjects increased monotonically with RT dose, between 1.05 ± 0.14 at 4 Gy and 1.58 ± 0.31 at 52 Gy. Subject No.111216172021RT dose and fractionation55Gy in 5 fractions. SBRT64 Gy in 32 fractions45 Gy in 15 fractions50 Gy in 20 fractions64 Gy in 32 fractions64 Gy in 32 fractionsTime between completion of RT and PET scan (weeks)822136714Gradient of relationship between PET uptake and RT dose0.0290.0050.0100.0060.0030.008Intercept1.3050.5040.8370.3910.6910.469r20.8410.5390.8360.8790.3100.672p value0.0280.1580.0300.0180.1630.089 A relationship between IMAFIB PET uptake and RT dose is consistent with RT dose-related activation of αvβ6 integrin in the irradiated lung and to the induction of lung fibrosis in subjects receiving pulmonary RT. Citation Format: Azeem Saleem, Yusuf Helo, Graham Searle, Fatjon Dekaj, Jo Cook, Zarni Win, Roger Gunn, Paula Wells. Imaging radiotherapy induced pulmonary fibrogenic changes with integrin-PET [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1144.