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

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, [F]-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 (<6 months after RT) had [F]-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) 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 (SUV) 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) and dose per RT fraction (r = 0.63; P < .001) and with BED for fibrosis (r = 0.38; P < .001 for α/β 3 Gy and r = 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.