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Clinical quantification of the integrin αvβ6 by [18F]FB-A20FMDV2 positron emission tomography in healthy and fibrotic human lung (PETAL Study)

Lukey, Pauline T.; Coello, Christopher; Gunn, Roger; Parker, Christine; Wilson, Frederick J.; Saleem, Azeem; Garman, Nadia; Costa, Maria; Kendrick, Stuart; Onega, Mayca; Kang’ombe, Arthur R.; Listanco, Allan; Davies, James; Ramada-Magalhaes, Joaquim; Moz, Sara; Fahy, William A.; Maher, Toby M.; Jenkins, Gisli; Passchier, Jan; Marshall, Richard P.

Authors

Pauline T. Lukey

Christopher Coello

Roger Gunn

Christine Parker

Frederick J. Wilson

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Dr Azeem Saleem A.Saleem@hull.ac.uk
Reader and Honorary Consultant in Clinical Oncology

Nadia Garman

Maria Costa

Stuart Kendrick

Mayca Onega

Arthur R. Kang’ombe

Allan Listanco

James Davies

Joaquim Ramada-Magalhaes

Sara Moz

William A. Fahy

Toby M. Maher

Gisli Jenkins

Jan Passchier

Richard P. Marshall



Abstract

© 2019, The Author(s). Purpose: The 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. Results: A 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. Conclusions: Lung uptake of [18F]FB-A20FMDV2, a measure of expression of the integrin αvβ6, was markedly increased in subjects with PF compared with healthy subjects.

Citation

Lukey, P. T., Coello, C., Gunn, R., Parker, C., Wilson, F. J., Saleem, A., …Marshall, R. P. (2020). Clinical quantification of the integrin αvβ6 by [18F]FB-A20FMDV2 positron emission tomography in healthy and fibrotic human lung (PETAL Study). European journal of nuclear medicine and molecular imaging, 47(4), 967-979. https://doi.org/10.1007/s00259-019-04586-z

Journal Article Type Article
Acceptance Date Oct 16, 2019
Online Publication Date Dec 9, 2019
Publication Date 2020-04
Deposit Date Feb 10, 2021
Publicly Available Date Mar 29, 2024
Journal European Journal of Nuclear Medicine and Molecular Imaging
Print ISSN 1619-7070
Electronic ISSN 1619-7089
Publisher Springer Verlag
Peer Reviewed Peer Reviewed
Volume 47
Issue 4
Pages 967-979
DOI https://doi.org/10.1007/s00259-019-04586-z
Keywords Idiopathic pulmonary fibrosis; [18F]FB-A20FMDV2 PET/CT; αvβ6 integrin; Biomarker; Pulmonary fibrosis; PET; Clinical study
Public URL https://hull-repository.worktribe.com/output/3630026

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Copyright Statement
© The Author(s) 2019. Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.






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