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Research ArticleOncology

18F-Fluoroestradiol Tumor Uptake Is Heterogeneous and Influenced by Site of Metastasis in Breast Cancer Patients

Hilde H. Nienhuis, Michel van Kruchten, Sjoerd G. Elias, Andor W.J.M. Glaudemans, Erik F.J. de Vries, Alfons H.H. Bongaerts, Carolien P. Schröder, Elisabeth G.E. de Vries and Geke A.P. Hospers
Journal of Nuclear Medicine August 2018, 59 (8) 1212-1218; DOI: https://doi.org/10.2967/jnumed.117.198846
Hilde H. Nienhuis
1Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
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Michel van Kruchten
1Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
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Sjoerd G. Elias
2Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands; and
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Andor W.J.M. Glaudemans
3Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
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Erik F.J. de Vries
3Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
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Alfons H.H. Bongaerts
3Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
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Carolien P. Schröder
1Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
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Elisabeth G.E. de Vries
1Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
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Geke A.P. Hospers
1Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
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Abstract

Heterogeneity of estrogen receptor (ER) expression in breast cancer is recognized. However, knowledge about varying expression across metastases and surrounding normal tissue in patients is scarce. We therefore analyzed 16α-18F-fluoro-17β-estradiol (18F-FES) PET to assess ER expression heterogeneity. Methods: 18F-FES PET on accredited PET/CT camera systems performed in patients with ER-positive metastatic breast cancer November 2009–December 2014 was analyzed. Lesions with an SUVmax 1.5 or more were considered ER-positive, but liver lesions were excluded given high background liver signal. CT lesions with a diameter 10 mm or more were included. We used multilevel linear-mixed models to evaluate determinants of 18F-FES uptake. Cluster analysis was performed with different imaging features per patient as input variables. Results: In 91 patients, 1,617 metastases in bone (78%), lymph node (15%), lung (4%), or liver (2%) were identified by CT (11.2%), PET (56.6%), or both (32.2%). Median tumor uptake varied greatly between patients (SUVmax, 0.54–14.21). 18F-FES uptake in bone metastases was higher than in lymph node and lung metastases (geometric mean SUVmax, 2.61 [95% confidence interval (CI), 2.31–2.94] vs. 2.29 [95% CI, 2.00–2.61; P < 0.001] vs. 2.23 [95% CI, 1.88–2.61; P = 0.021]), respectively. Cluster analysis identified 3 subgroups of patients characterized by particular metastatic sites and 18F-FES PET/CT features. SUVmax in surrounding normal tissue, highest in the bones, varied per patient (range, 0.7–3.3). Conclusion: 18F-FES uptake is heterogeneous in tumor and normal tissue and influenced by anatomic site. Different patterns can be distinguished, possibly identifying biologically relevant ER-positive metastatic breast cancer patient subgroups.

  • breast cancer
  • estrogen receptor
  • 18F-fluoroestradiol PET
  • tumor heterogeneity
  • tumor microenvironment

Footnotes

  • ↵† Deceased.

  • Published online Mar. 30, 2018.

  • © 2018 by the Society of Nuclear Medicine and Molecular Imaging.
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Journal of Nuclear Medicine: 59 (8)
Journal of Nuclear Medicine
Vol. 59, Issue 8
August 1, 2018
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18F-Fluoroestradiol Tumor Uptake Is Heterogeneous and Influenced by Site of Metastasis in Breast Cancer Patients
Hilde H. Nienhuis, Michel van Kruchten, Sjoerd G. Elias, Andor W.J.M. Glaudemans, Erik F.J. de Vries, Alfons H.H. Bongaerts, Carolien P. Schröder, Elisabeth G.E. de Vries, Geke A.P. Hospers
Journal of Nuclear Medicine Aug 2018, 59 (8) 1212-1218; DOI: 10.2967/jnumed.117.198846

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18F-Fluoroestradiol Tumor Uptake Is Heterogeneous and Influenced by Site of Metastasis in Breast Cancer Patients
Hilde H. Nienhuis, Michel van Kruchten, Sjoerd G. Elias, Andor W.J.M. Glaudemans, Erik F.J. de Vries, Alfons H.H. Bongaerts, Carolien P. Schröder, Elisabeth G.E. de Vries, Geke A.P. Hospers
Journal of Nuclear Medicine Aug 2018, 59 (8) 1212-1218; DOI: 10.2967/jnumed.117.198846
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Keywords

  • breast cancer
  • estrogen receptor
  • 18F-fluoroestradiol PET
  • tumor heterogeneity
  • tumor microenvironment
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