Integrin-PET uptake evaluation in patients receiving pulmonary radiotherapy

Objectives: Integrin αvβ6, an epithelial-specific integrin is not expressed in healthy adult epithelia but is upregulated during wound healing, in cancer and activates Transforming Growth Factor (TGF). TGF β-1, which plays a key role in the fibrotic pathway. Pre-clinical studies have demonstrated that αvβ6 integrin expression in alveolar epithelium increases after radiotherapy (RT) before onset of fibrosis, and anti- αvβ6 therapy prevents fibrogenesis [1]. Lung fibrosis presents as progressive pulmonary injury and is a major barrier to improved cure rate after pulmonary radiotherapy in patients with non-small cell lung cancer (NSCLC). In this study, the utility of PET imaging with a αvβ6 integrin ligand was evaluated in patients with non-small cell lung cancer following pulmonary RT. Subjects with NSCLC 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. Six subjects (3M; 3F) 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. Five subjects received conformal external beam RT, while one subject received stereotactic RT (SBRT). Biological effective doses (BED) using the linear quadratic cell survival radiobiology model [2] were calculated for pneumonitis (α/β = 5) and lung fibrosis (α/β = 3). The averaged normalised SUV across all subjects increased monotonically with RT dose (figure), between 1.05 ± 0.14 at 4 Gy and 1.58 ± 0.31 at 52 Gy. A correlation between a higher IMAFIB 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, all of whom received hypo-fractionated RT regimens (table).

[asterisk]BED not calculated (NC) for SBRT regimen. 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.

• Download figure
• Open in new tab
• Download powerpoint