Integrin αvβ6 Positron Emission Tomography Imaging in Lung Cancer Patients Treated With Pulmonary Radiation Therapy.

Abstract

Post radiation therapy (RT) lung fibrosis is a major barrier to improved cure rate in lung cancer. Integrin αvβ6 plays a key role in fibrogenesis by activating transforming growth factor-β. Positron emission tomography (PET) studies with a fluorine-18 radiolabelled αvβ6 radioligand, [¹⁸F]-FBA-A20FMDV2, were performed to assess uptake, and the relationship to RT dose parameters was explored. Recently treated non-small cell lung cancer patients (<6 months after RT) had [¹⁸F]-FBA-A20FMDV2-PET scans, coregistered with the RT planning computed tomography and segmented to RT doses of >40 Gy (excluding tumor), 25 to 40 Gy, 15 to 25 Gy, 8 to 15 Gy, and <8 Gy. PET uptake (standardized uptake value; SUV) corrected for tissue density between 10 and 60 minutes (SUV_10-60) was calculated and compared with RT dose, dose per fraction, and biological effective dose (BED). PET uptake was also evaluated in healthy volunteers. Six non-small cell lung cancer (3 male; 3 female) subjects scanned between 6 and 22 weeks after RT and 6 healthy volunteers (3 males; 3 females) were evaluated. Higher mean PET uptake (SUV_10-60) was observed in the irradiated lung compared with the healthy lung (2.97 vs 1.99; P < .05). A significant and positive pharmacodynamic relationship was observed between radioligand uptake (SUV_10-60) and dose per RT fraction (r² = 0.63; P < .001) and with BED for fibrosis (r² = 0.38; P < .001 for α/β 3 Gy and r² = 0.33; P < 0.001 for α/β 5 Gy). Higher uptake in the irradiated lung and a pharmacodynamic relationship between αvβ6 radioligand uptake versus RT dose per fraction and BED for lung fibrosis is consistent with RT induced activation of αvβ6 integrin and supports a role for αvβ6 in the induction of lung fibrosis after pulmonary RT. αvβ6-PET imaging may potentially aid in the assessment and management of radiation-induced pulmonary fibrosis.