Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
European Journal of Nuclear Medicine and Molecular Imaging
Published in: European Journal of Nuclear Medicine and Molecular Imaging 5/2018

Open Access 01-05-2018 | Original Article

Pulmonary 18F-FDG uptake helps refine current risk stratification in idiopathic pulmonary fibrosis (IPF)

Authors: Thida Win, Nicholas J. Screaton, Joanna C. Porter, Balaji Ganeshan, Toby M. Maher, Francesco Fraioli, Raymondo Endozo, Robert I. Shortman, Lynn Hurrell, Beverley F. Holman, Kris Thielemans, Alaleh Rashidnasab, Brian F. Hutton, Pauline T. Lukey, Aiden Flynn, Peter J. Ell, Ashley M. Groves

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 5/2018

Login to get access

Abstract

Purpose

There is a lack of prognostic biomarkers in idiopathic pulmonary fibrosis (IPF) patients. The objective of this study is to investigate the potential of 18F-FDG-PET/ CT to predict mortality in IPF.

Methods

A total of 113 IPF patients (93 males, 20 females, mean age ± SD: 70 ± 9 years) were prospectively recruited for 18F-FDG-PET/CT. The overall maximum pulmonary uptake of 18F-FDG (SUVmax), the minimum pulmonary uptake or background lung activity (SUVmin), and target-to-background (SUVmax/ SUVmin) ratio (TBR) were quantified using routine region-of-interest analysis. Kaplan–Meier analysis was used to identify associations of PET measurements with mortality. We also compared PET associations with IPF mortality with the established GAP (gender age and physiology) scoring system. Cox analysis assessed the independence of the significant PET measurement(s) from GAP score. We investigated synergisms between pulmonary 18F-FDG-PET measurements and GAP score for risk stratification in IPF patients.

Results

During a mean follow-up of 29 months, there were 54 deaths. The mean TBR ± SD was 5.6 ± 2.7. Mortality was associated with high pulmonary TBR (p = 0.009), low forced vital capacity (FVC; p = 0.001), low transfer factor (TLCO; p < 0.001), high GAP index (p = 0.003), and high GAP stage (p = 0.003). Stepwise forward-Wald–Cox analysis revealed that the pulmonary TBR was independent of GAP classification (p = 0.010). The median survival in IPF patients with a TBR < 4.9 was 71 months, whilst in those with TBR > 4.9 was 24 months. Combining PET data with GAP data (“PET modified GAP score”) refined the ability to predict mortality.

Conclusions

A high pulmonary TBR is independently associated with increased risk of mortality in IPF patients.
Appendix
Available only for authorised users
Literature
1.
Coultas DB, Zumwalt RE, Black WC, Sobonya RE. The epidemiology of interstitial lung diseases. Am J Resp Crit Care Med. 1994;150:967–72.CrossRefPubMed
2.
Joint Statement of the American Thoracic Society (ATS), and the European Respiratory Society (ERS). American Thoracic Society/European Respiratory Society international multidisciplinary consensus classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med. 2002;165:277–304.CrossRef
3.
Spagnolo P, Maher TM. Clinical trial research in focus: why do so many clinical trials fail in IPF? Lancet Respiratory. 2017;5:372–4.CrossRef
4.
5.
Jones HA, Cadwallader KA, White JF, Uddin M, Peters AM, Chilvers ER. Dissociation between respiratory burst activity and deoxyglucose uptake in human neutrophil granulocytes: implications for interpretation of 18F-FDG PET images. J Nucl Med. 2002;43:652–7.PubMed
6.
Wallace WE, Gupta NC, Hubbs AF, Mazza SM, Bishop HA, Keane MJ, et al. Cis-4-[18F]fluoro-l-proline PET imaging of pulmonary fibrosis in a rabbit model. J Nucl Med. 2002;43:413–20.PubMed
7.
Chen DL, Schuster DP. Imaging pulmonary inflammation with positron emission tomography: a biomarker for drug development. Mol Pharm. 2006;3:488–95.CrossRefPubMed
8.
Groves AM, Win T, Screaton NJ, Berovic M, Endozo R, Booth H, et al. Idiopathic pulmonary fibrosis and diffuse Parenchymal lung disease: implications from initial experience with 18F-FDG-PET/CT. J Nucl Med. 2009;50:538–45.CrossRefPubMed
9.
Win T, Lambrou T, Hutton BF, Kayani I, Screaton NJ, Porter JC, et al. 18F-Fluorodeoxyglucose positron emission tomography pulmonary imaging in idiopathic pulmonary fibrosis is reproducible: implications for future clinical trials. Eur J Nucl Med Mol Imaging. 2012;39:521–8.CrossRefPubMed
10.
Ahluwalia N, Shea BS, Tager AM. New therapeutic targets in idiopathic pulmonary fibrosis. Aiming to rein in runaway wound-healing responses. Am J Respir Crit Care Med. 2014;190:867–78.CrossRefPubMedPubMedCentral
11.
12.
13.
14.
Noble PW, Albera C, Bradford WZ, Costabel U, Glassberg MK, Kardatzke D, et al. Pirfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): two randomised trials. Lancet. 2011;377:1760–9.CrossRefPubMed
15.
Richeldi L, du Bois RM, Raghu G, Azuma A, Brown KK, Costabel U, et al. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med. 2014;370:2071–82.CrossRefPubMed
16.
Ley B, Ryerson CJ, Vittinghoff E, Ryu JH, Tomassetti S, Lee JS, et al. A multidimensional index and staging system for idiopathic pulmonary fibrosis. Ann Intern Med. 2012;15(156):684–91.CrossRef
17.
Hunter GJ, Hamberg LM, Alpert NM, Choi NC, Fischman AJ. Simplified measurement of deoxyglucose utilization rate. J Nucl Med. 1996 Jun;37(6):950–5.PubMed
18.
Krak NC, van der Hoeven JJ, Hoekstra OS, Twisk JW, van der Wall E, Lammertsma AA. Measuring [(18)F]FDG uptake in breast cancer during chemotherapy: comparison of analytical methods. Eur J Nucl Med Mol Imaging. 2003;30(5):674–81.CrossRefPubMed
19.
Chen DL, Mintun MA, Schuster DP. Comparison of methods to quantitate 18F-FDG uptake with PET during experimental acute lung injury. J Nucl Med. 2004;45(9):1583–90.PubMed
20.
Bucerius J, Hyafil F, Verberne HJ, Slart RH, Lindner O, Sciagra R, et al. Cardiovascular Committee of the European Association of Nuclear Medicine (EANM). Position paper of the cardiovascular Committee of the European Association of Nuclear Medicine (EANM) on PET imaging of atherosclerosis. Eur J Nucl Med Mol Imaging. 2016;43(4):780–9.CrossRefPubMed
21.
Faraggi D, Simon R. A simulation study of cross-validation for selecting an optimal cutpoint in univariate survival analysis. Stat Med. 1996;15:2203–13.CrossRefPubMed
22.
Raghu G, Collard HR, Anstrom KJ, Flaherty KR, Fleming TR, King TE, et al. Idiopathic pulmonary fibrosis: clinically meaningful primary endpoints in phase 3 clinical trials. Am J Respir Crit Care Med. 2012;185:1044–8.CrossRefPubMedPubMedCentral
23.
Wells AU, Desai SR, Rubens MB, Goh NS, Cramer D, Nicholson AG, et al. Idiopathic pulmonary fibrosis: a composite physiologic index derived from disease extent observed by computed tomography. Am J Respir Crit Care Med. 2003;167:962–9.CrossRefPubMed
24.
Jenkins RG, Simpson JK, Saini G, Bentley JH, Russell AM, Braybrooke R, et al. Longitudinal change in collagen degradation biomarkers in idiopathic pulmonary fibrosis: an analysis from the prospective, multicentre PROFILE study. Lancet Respir Med. 2015;3:462–72.CrossRefPubMed
25.
Wells AU, Behr J, Costabel U, Cottin V, Poletti V, Richeldi L. Hot of the breath: mortality as a primary end-point in IPF treatment trials: the best is the enemy of the good. Thorax. 2012;67:938–40.CrossRefPubMed
26.
Fujimoto K, Taniguchi H, Johkoh T, Kondoh Y, Ichikado K, Sumikawa H, et al. Acute exacerbation of idiopathic pulmonary fibrosis: high-resolution CT scores predict mortality. Eur Radiol. 2012;22:83–92.CrossRefPubMed
27.
Akira M, Kozuka T, Yamamoto S, Sakatani M. Computed tomographic findings in acute exacerbation of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2008;178:372–8.CrossRefPubMed
28.
Mogulkoc N, Brutsche MH, Bishop PW, Greaves SM, Horrocks AW, Egan JJ, et al. Pulmonary function in idiopathic pulmonary fibrosis and referral for lung transplantation. Am J Respir Crit Care Med. 2001;164:103–8.CrossRefPubMed
29.
Lynch DA, Godwin JD, Safrin S, Starko KM, Hormel P, Brown KK, et al. Idiopathic pulmonary fibrosis study group. High-resolution computed tomography in idiopathic pulmonary fibrosis: diagnosis and prognosis. Am J Respir Crit Care Med. 2005;172:488–93.CrossRefPubMed
30.
Gay SE, Kazerooni EA, Toews GB, Lynch JP III, Gross BH, Cascade PH, et al. Idiopathic pulmonary fibrosis: predicting response to therapy and survival. Am J Respir Crit Care Med. 1998;157:1063–72.CrossRefPubMed
31.
Humphries SM, Yagihashi K, Huckleberry J, Rho BH, Schroeder JD, Strand M, et al. Idiopathic pulmonary fibrosis: data-driven textural analysis of extent of fibrosis at baseline and 15-month follow-up. Radiology. 2017;10:16117. [Epub ahead of print]
32.
Jacob J, Bartholmai BJ, Rajagopalan S, Kokosi M, Nair A, Karwoski R, et al. Mortality prediction in idiopathic pulmonary fibrosis: evaluation of computer-based CT analysis with conventional severity measures. Eur Respir J. 2017. 49(1).
33.
Moon JW, Bae JP, Lee HY, Kim N, Chung MP, Park HY, et al. Perfusion- and pattern-based quantitative CT indexes using contrast-enhanced dual-energy computed tomography in diffuse interstitial lung disease: relationships with physiologic impairment and prediction of prognosis. Eur Radiol. 2016;26:1368–77.CrossRefPubMed
34.
Groves AM, Win T, Haim SB, Ell PJ. Non-[18F] FDG PET in clinical oncology. Lancet Oncol. 2007;8:822–30.CrossRefPubMed
35.
Lambrou T, Groves AM, Erlandsson K, Screaton N, Endozo R, Win T, et al. The importance of correction for tissue fraction effects in lung PET: preliminary findings. Eur J Nucl Med Mol Imaging. 2011;3812:2238–46.CrossRef
36.
Nobashi T, Kubo T, Nakamoto Y, Handa T, Koyasu S, Ishimori T, et al. FDG uptake in less affected lung field provides prognostic stratification in patients with interstitial lung disease. J Nucl Med. 2016;57:1899–904.CrossRefPubMed
37.
Win T, Thomas BA, Lambrou T, Hutton BF, Screaton NJ, Porter JC, et al. Areas of normal pulmonary parenchyma on HRCT exhibit increased FDG PET signal in IPF patients. Eur J Nucl Med Mol Imaging. 2014;41:337–42.CrossRefPubMed
38.
Andrianifahanana M, Hernandez DM, Yin X, Kang JH, Jung MY, Wang Y, et al. Profibrotic up-regulation of glucose transporter 1 by TGF-β involves activation of MEK and mammalian target of rapamycin complex 2 pathways. FASEB J. 2016;30(11):3733–44.CrossRefPubMedPubMedCentral
39.
Kottmann RM, Kulkarni AA, Smolnycki KA, Lyda E, Dahanayake T, Salibi R, et al. Lactic acid is elevated in idiopathic pulmonary fibrosis and induces myofibroblast differentiation via pH-dependent activation of transforming growth factor-beta. Am J Respir Crit Care Med. 2012;186:740–51.CrossRefPubMedPubMedCentral
40.
Holman BF, Cuplov V, Hutton BF, Groves AM, Thielemans K. The effect of respiratory induced density variations on non-TOF PET quantitation in the lung. Phys Med Biol. 2016;61:3148–63.CrossRefPubMed
41.
Chen DL, Cheriyan J, Chilvers ER, Choudhury G, Coello C, Connell M, et al. Quantification of lung PET images: challenges and opportunities. J Nucl Med. 2017;58:201–7.CrossRefPubMedPubMedCentral
42.
Holman BF, Cuplov V, Millner L, Hutton BF, Maher TM, Groves AM, et al. Improved correction for the tissue fraction effect in lung PET/CT imaging. Phys Med Biol. 2015;60:7387–402.CrossRefPubMed
43.
Umeda Y, Demura Y, Morikawa M, Anzai M, Kadowaki M, Ameshima S, et al. Prognostic value of dual-time-point 18F-FDG PET for idiopathic pulmonary fibrosis. J Nucl Med. 2015;56:1869–75.CrossRefPubMed
44.
Justet A, Laurent-Bellue A, Thabut G, Dieudonne A, Debray MP, Borie R, et al. [18F]FDG PET/CT predicts progression-free survival in patients with idiopathic pulmonary fibrosis. 2017. Respir Res. 2017;18:74.CrossRefPubMedPubMedCentral
Metadata
Title
Pulmonary 18F-FDG uptake helps refine current risk stratification in idiopathic pulmonary fibrosis (IPF)
Authors
Thida Win
Nicholas J. Screaton
Joanna C. Porter
Balaji Ganeshan
Toby M. Maher
Francesco Fraioli
Raymondo Endozo
Robert I. Shortman
Lynn Hurrell
Beverley F. Holman
Kris Thielemans
Alaleh Rashidnasab
Brian F. Hutton
Pauline T. Lukey
Aiden Flynn
Peter J. Ell
Ashley M. Groves
Publication date
01-05-2018
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 5/2018
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-017-3917-8

Other articles of this Issue 5/2018

European Journal of Nuclear Medicine and Molecular Imaging 5/2018 Go to the issue

Original Article

The diagnostic value of 18F–FDG-PET/CT and MRI in suspected vertebral osteomyelitis – a prospective study

Reply

Reply: Interim FDG-PET/CT in primary mediastinal diffuse large B-cell lymphoma: really almost useless procedure?

Editorial Commentary

Combining baseline TMTV and gene profiling for a better risk stratification in diffuse large B cell lymphoma

Original Article

Prediction of outcome using pretreatment 18F-FDG PET/CT and MRI radiomics in locally advanced cervical cancer treated with chemoradiotherapy

Original Article

Superiority of 68Ga-DOTATATE over 18F-FDG and anatomic imaging in the detection of succinate dehydrogenase mutation (SDHx )-related pheochromocytoma and paraganglioma in the pediatric population

Original Article

Comparison of positron emission tomography/computed tomography and magnetic resonance imaging for posttherapy evaluation in patients with advanced cervical cancer receiving definitive concurrent chemoradiotherapy