Abstract
PurposeThe RGD-integrin, αvβ6, plays a role in the pathogenesis of pulmonary fibrosis through activation of transforming growth factor beta (TGFβ). This study sought to quantify expression of αvβ6 in the lungs of healthy humans and subjects with pulmonary fibrosis using the αvβ6-selective [18F]FB-A20FMDV2 PET ligand.Methods[18F]FB-A20FMDV2 PET/CT scans were performed in healthy subjects and those with fibrotic lung disease. Standard uptake values (SUV) and volume of distribution (VT) were used to quantify αvβ6 expression. In subjects with fibrotic lung disease, qualitative assessment of the relationship between αvβ6 expression and the distribution of fibrosis on high resolution computed tomography was conducted.ResultsA total of 15 participants (6 healthy, 7 with idiopathic pulmonary fibrosis (IPF) and 2 with connective tissue disease (CTD) associated PF) were enrolled. VT and SUV of [18F]FB-A20FMDV2 were increased in the lungs of subjects with pulmonary fibrosis (PF) compared with healthy subjects. Geometric mean VT (95% CI) was 0.88 (0.60, 1.29) mL/cm3 for healthy subjects, and 1.40 (1.22, 1.61) mL/cm3 for subjects with IPF; and SUV was 0.54 (0.36, 0.81) g/mL for healthy subjects and 1.03 (0.86, 1.22) g/mL for subjects with IPF. The IPF/healthy VT ratio (geometric mean, (95% CI of ratio)) was 1.59 (1.09, 2.32) (probability ratio > 1 = 0.988)) and the SUV ratio was 1.91 (1.27, 2.87) (probability ratio > 1 = 0.996). Increased uptake of [18F]FB-A20FMDV2 in PF was predominantly confined to fibrotic areas. [18F]FB-A20FMDV2 measurements were reproducible at an interval of 2 weeks. [18F]FB-A20FMDV2 was safe and well tolerated.ConclusionsLung uptake of [18F]FB-A20FMDV2, a measure of expression of the integrin αvβ6, was markedly increased in subjects with PF compared with healthy subjects.
Highlights
Idiopathic pulmonary fibrosis (IPF) is a chronic progressive scarring of the lungs of unknown aetiology
We investigated the potential for [18F]FBA20FMDV2 to safely and reproducibly quantify αvβ6 integrins in the lungs of healthy subjects as well as those with pulmonary fibrosis due to IPF or connective tissue disease (CTD)-interstitial lung disease (ILD)
The study was approved by the London–Brent Research Ethics Committee, UK, and permission to administer radioisotopes was obtained from the Administration of Radioactive Substances Advisory Committee (ARSAC) of the UK (Ref: 630/3925/30809)
Summary
Lung uptake of [18F]FB-A20FMDV2, a measure of expression of the integrin αvβ, was markedly increased in subjects with PF compared with healthy subjects.
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