%0 Journal Article %A Hilde H. Nienhuis %A Michel van Kruchten %A Sjoerd G. Elias %A Andor W.J.M. Glaudemans %A Erik F.J. de Vries %A Alfons H.H. Bongaerts %A Carolien P. Schröder %A Elisabeth G.E. de Vries %A Geke A.P. Hospers %T 18F-Fluoroestradiol Tumor Uptake Is Heterogeneous and Influenced by Site of Metastasis in Breast Cancer Patients %D 2018 %R 10.2967/jnumed.117.198846 %J Journal of Nuclear Medicine %P 1212-1218 %V 59 %N 8 %X 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. %U https://jnm.snmjournals.org/content/jnumed/59/8/1212.full.pdf