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

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
EJNMMI Research
Published in: EJNMMI Research 1/2019

Open Access 01-12-2019 | Positron Emission Tomography | Original research

Enhanced pulmonary uptake on 18F-FES-PET/CT scans after irradiation of the thoracic area: related to fibrosis?

Authors: C. M. Venema, E. F. J. de Vries, S. J. van der Veen, M. D. Dorrius, M. van Kruchten, C. P. Schröder, G. A. P. Hospers, A. W. J. M. Glaudemans

Published in: EJNMMI Research | Issue 1/2019

Login to get access

Abstract

Rationale

The use of 16α-[18F]fluoro-17β-estradiol (FES) positron emission tomography (PET) in clinical dilemmas and for therapy decision-making in lesions expressing estrogen receptors is growing. However, on a considerable number of FES PET scans, previously performed in a research and clinical setting in our institution, FES uptake was noticed in the lungs without an oncologic substrate. We hypothesized that this uptake was related to pulmonary fibrosis as a result of radiation therapy. This descriptive study therefore aimed to investigate whether radiation therapy in the thoracic area is possibly related to enhanced pulmonary, non-tumor FES uptake.

Methods

All FES-PET/CT scans performed in our institution from 2008 to 2017 were retrospectively analyzed. Scans from patients who had received irradiation in the thoracic area prior to the scan were compared to scans of patients who had never received irradiation in the thoracic area. The primary outcome was the presence of enhanced non-tumor FES uptake in the lungs, defined as visually increased FES uptake in the absence of an oncologic substrate on the concordant (contrast-enhanced) CT scan. All CT scans were evaluated for the presence of fibrosis or oncologic substrates.

Results

A total of 108 scans were analyzed: 70 scans of patients with previous irradiation in the thoracic area and 38 of patients without. Enhanced non-tumor FES uptake in the lungs was observed in 39/70 irradiated patients (56%), versus in 9/38 (24%) of non-irradiated patients. Fibrosis was present in 37 of the 48 patients with enhanced non-tumor FES uptake (77%), versus in 15 out of 60 (25%) patients without enhanced non-tumor uptake, irrespective of radiotherapy (p < 0.001).

Conclusion

After irradiation of the thorax, enhanced non-tumor uptake on FES-PET can be observed in the radiation field in a significant proportion of patients. This seems to be related to fibrosis. When observing enhanced FES uptake in the lungs, this should not be interpreted as metastases. Information on recent radiation therapy or history of pulmonary fibrosis should therefore be taken into consideration.
Literature
1.
Cardoso F, Harbeck N, Fallowfield L, Kyriakides S, Senkus E, ESMO Guidelines Working Group. Locally recurrent or metastatic breast cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012;23(S7):vii11–9.PubMed
2.
Allred DC, Harvey JM, Berardo M, Clark GM. Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol. 1998;11:155–8.PubMed
3.
Simmons C, Miller N, Geddie W, et al. Does confirmatory tumor biopsy alter the management of breast cancer patients with distant metastases? Ann Oncol. 2009;20:1499–504.CrossRef
4.
Dehdashti F, Mortimer JE, Trinkaus K, et al. PET-based estradiol challenge as a predictive biomarker of response to endocrine therapy in women with estrogen-receptor-positive breast cancer. Breast Cancer Res Treat. 2009;113:509–17.CrossRef
5.
Kurland BF, Peterson LM, Lee JH, et al. Between-patient and within-patient (site-to-site) variability in estrogen receptor binding, measured in vivo by 18F-fluoroestradiol PET. J Nucl Med. 2001;52:1541–9.CrossRef
6.
Linden HM, Kurland BF, Peterson LM, et al. Fluoroestradiol positron emission tomography reveals differences in pharmacodynamics of aromatase inhibitors, tamoxifen, and fulvestrant in patients with metastatic breast cancer. Clin Cancer Res. 2011;17:4799–805.CrossRef
7.
Linden HM, Stekhova SA, Link JM, et al. Quantitative fluoroestradiol positron emission tomography imaging predicts response to endocrine treatment in breast cancer. J Clin Oncol. 2006;24:2793–9.CrossRef
8.
Peterson LM, Kurland BF, Schubert EK, et al. A phase 2 study of 16α-[18F]-fluoro-17β-estradiol positron emission tomography (FES-PET) as a marker of hormone sensitivity in metastatic breast cancer (MBC). Mol Imaging Biol. 2014;16:431–40.CrossRef
9.
Peterson LM, Kurland BF, Link JM, et al. Factors influencing the uptake of 18F-fluoroestradiol in patients with estrogen receptor positive breast cancer. Nucl Med Biol. 2011;38:969–78.CrossRef
10.
van Kruchten M, de Vries EG, Glaudemans AW, et al. Measuring residual estrogen receptor availability during fulvestrant therapy in patients with metastatic breast cancer. Cancer Discov. 2015;5:72–81.CrossRef
11.
van Kruchten M, Glaudemans AW, de Vries EF, et al. PET imaging of estrogen receptors as a diagnostic tool for breast cancer patients presenting with a clinical dilemma. J Nucl Med. 2012;53:182–90.CrossRef
12.
Seimbille Y, Rousseau J, Benard F, et al. 18F-labeled difluoroestradiols: preparation and preclinical evaluation as estrogen receptor-binding radiopharmaceuticals. Steroids. 2002;67:765–75.CrossRef
13.
Yoo J, Dence CS, Sharp TL, Katzenellenbogen JA, Welch MJ. Synthesis of an estrogen receptor β-selective radioligand: 5-[18F]fluoro-(2R,3S)-2,3-bis(4-hydroxyphenyl) pentanenitrile and comparison of in vivo distribution with 16α-[18F]fluoro-17β-estradiol. J Med Chem. 2005;48:6366–78.CrossRef
14.
van Kruchten M, de Vries EG, Brown M, et al. PET imaging of oestrogen receptors in patients with breast cancer. Lancet Oncol. 2013;14:e465–75.CrossRef
15.
Venema CM, Apollonio G, Hospers GAP, et al. Recommendations and technical aspects of 16α-[18F]fluoro-17β-estradiol PET to image the estrogen receptor in vivo: the Groningen experience. Clin Nucl Med. 2016;41:844–51.CrossRef
16.
Boellaard R, Delgado-Bolton R, Oyen WJ, et al. FDG PET/CT: EANM procedure guidelines for tumour imaging: version 2.0. Eur J Nucl met. Mol Imaging. 2015;42:328–54.
17.
van Kruchten M, de Vries EF, Arts HJ, et al. Assessment of estrogen receptor expression in epithelial ovarian cancer patients using 16α-[18F]fluoro-17β-estradiol PET/CT. J Nucl Med. 2015;56:50–5.CrossRef
18.
Couse JF, Lindzey J, Grandien K, Gustafsson JA, Korach KS. Tissue distribution and quantitative analysis of estrogen receptor-α (ERα) and estrogen receptor-β (ERβ) messenger ribonucleic acid in the wild-type and ERα-knockout mouse. Endocrinology. 1997;138:4613–21.CrossRef
19.
Chotirmall SJ, Greene MC, Oglesby IK, et al. 17β estradiol inhibits IL-8 in cystic fibrosis by upregulating secretory leucoprotease inhibitor. Am J Respir Crit Care Med. 2010;182:62–72.CrossRef
20.
Taniuchi S, Fujishima F, Miki Y, et al. Tissue concentrations of estrogens and aromatase immunolocalization in interstitial pneumonia of human lung. Mol Cell Endocrinol. 2014;392:136–43.CrossRef
21.
Douin-Echinard V, Laffont S, Seillet C, et al. Estrogen receptor α, but not β, is required for optimal dendritic cell differentiation and CD40-induced cytokine production. J Immunol. 2008;180:3661–9.CrossRef
22.
Lammertyn EJ, Vandermeulen E, Bellon H, et al. End-stage cystic fibrosis lung disease is characterised by a diverse inflammatory pattern: an immunohistochemical analysis. Respir Res. 2017;18:10.CrossRef
23.
Haviland JS, Owen JR, Dewar JA, et al. The UK standardisation of breast radiotherapy (START) trials of radiotherapy hypofractionation for treatment of early breast cancer: 10-years follow-up results of two randomised controlled trials. Lancet Oncol. 2013;11:1086–94.CrossRef
24.
Choi YW, Munden RF, Erasmus JJ, et al. Effects of radiation therapy on the lung: radiologic appearances and differential diagnosis. Radiographics. 2004;24:985–97.CrossRef
25.
Barnett GC, West CM, Dunning AM, et al. Normal tissue reactions to radiotherapy: towards tailoring treatment dose by genotype. Nat Rev Cancer. 2009;9:134–42.CrossRef
26.
Cohen Y, Gellei B, Robinson E. Bilateral radiation pneumonitis after unilateral lung and mediastinal irradiation. Radiol Clin Biol. 1974;43:465–71.PubMed
27.
Martin C, Romero S, Sanchez-Paya J, Massuti B, Arriero JM, Hernandez L. Bilateral lymphocytic alveolitis: a common reaction after unilateral thoracic irradiation. Eur Respir J. 1999;13:727–32.CrossRef
28.
Coppes RP, Muijs CT, Faber H, et al. Volume-dependent expression of in-field and out-of-field effects in the proton-irradiated rat lung. Int J Radiat Oncol Biol Phys. 2011;81:262–9.CrossRef
29.
van der Veen SJ, Faber H, Ghobadi G, et al. Decreasing irradiated rat lung volume changes dose-limiting toxicity from early to late effects. Int J Radiat Oncol Biol Phys. 2016;94:163–71.CrossRef
30.
Ghobadi G, Bartelds B, van der Veen SJ, et al. Lung irradiation induces pulmonary vascular remodelling resembling pulmonary arterial hypertension. Thorax. 2012;67:334–41.CrossRef
Metadata
Title
Enhanced pulmonary uptake on 18F-FES-PET/CT scans after irradiation of the thoracic area: related to fibrosis?
Authors
C. M. Venema
E. F. J. de Vries
S. J. van der Veen
M. D. Dorrius
M. van Kruchten
C. P. Schröder
G. A. P. Hospers
A. W. J. M. Glaudemans
Publication date
01-12-2019
Publisher
Springer Berlin Heidelberg
Published in
EJNMMI Research / Issue 1/2019
Electronic ISSN: 2191-219X
DOI
https://doi.org/10.1186/s13550-019-0549-y

Other articles of this Issue 1/2019

EJNMMI Research 1/2019 Go to the issue

Short communication

Voxel-based correlation of 18F-THK5351 accumulation and gray matter volume in the brain of cognitively normal older adults

Original research

Impact of acquisition time and penalizing factor in a block-sequential regularized expectation maximization reconstruction algorithm on a Si-photomultiplier-based PET-CT system for 18F-FDG

Short communication

Validation of [125I]CPCR4.3 as an investigative tool for the sensitive and specific detection of hCXCR4 and mCXCR4 expression in vitro and in vivo

Original research

Evaluation of data-driven respiratory gating waveforms for clinical PET imaging

Original research

Correlation between 18F-1-amino-3-fluorocyclobutane-1-carboxylic acid (18F-fluciclovine) uptake and expression of alanine-serine-cysteine-transporter 2 (ASCT2) and L-type amino acid transporter 1 (LAT1) in primary prostate cancer

Original research

Targeting mannose receptor expression on macrophages in atherosclerotic plaques of apolipoprotein E-knockout mice using 68Ga-NOTA-anti-MMR nanobody: non-invasive imaging of atherosclerotic plaques