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

Saleem, Azeem; Helo, Yusuf; Win, Zarni; Dale, Roger; Cook, Jo; Searle, Graham E.; Wells, Paula

Abstract

© 2020 Elsevier Inc. Purpose: 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.

Methods and Materials: Recently treated non-small cell lung cancer patients (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 (SUV10-60) was calculated and compared with RT dose, dose per fraction, and biological effective dose (BED). PET uptake was also evaluated in healthy volunteers.

Results
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 (SUV10-60) 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 (SUV10-60) 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).

Conclusions
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.

Citation

Saleem, A., Helo, Y., Win, Z., Dale, R., Cook, J., Searle, G. E., & Wells, P. (2020). Integrin αvβ6 Positron Emission Tomography Imaging in Lung Cancer Patients Treated With Pulmonary Radiation Therapy. International journal of radiation oncology, biology, physics, 107(2), 370-376. https://doi.org/10.1016/j.ijrobp.2020.02.014

• Journal Article Type: Article
• Acceptance Date: Feb 2, 2020
• Online Publication Date: Feb 11, 2020
• Publication Date: Jun 1, 2020
• Deposit Date: Jan 20, 2021
• Journal: International Journal of Radiation Oncology Biology Physics
• Print ISSN: 0360-3016
• Electronic ISSN: 1879-355X
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 107
• Issue: 2
• Pages: 370-376
• DOI: https://doi.org/10.1016/j.ijrobp.2020.02.014
• Keywords: Cancer Research; Oncology; Radiation; Radiology Nuclear Medicine and imaging
• Public URL: https://hull-repository.worktribe.com/output/3551071
• Related Public URLs: https://www.sciencedirect.com/science/article/abs/pii/S036030162030184X