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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- 18 F-fluoro-17β-estradiol ( 18 F-FES) PET to assess ER expression heterogeneity. Methods:  18 F-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 SUV max 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 18 F-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 (SUV max , 0.54-14.21). 18 F-FES uptake in bone metastases was higher than in lymph node and lung metastases (geometric mean SUV max , 2.61 [95% confidence interval (CI), 2.31-2.94] vs. 2.29 [95% CI, 2.00-2.61; P &lt; 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 18 F-FES PET/CT features. SUV max in surrounding normal tissue, highest in the bones, varied per patient (range, 0.7-3.3). Conclusion:  18 F-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.

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

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