@article {Nienhuis1212, author = {Hilde H. Nienhuis and Michel van Kruchten and Sjoerd G. Elias and Andor W.J.M. Glaudemans and Erik F.J. de Vries and Alfons H.H. Bongaerts and Carolien P. Schr{\"o}der and Elisabeth G.E. de Vries and Geke A.P. Hospers}, title = {18F-Fluoroestradiol Tumor Uptake Is Heterogeneous and Influenced by Site of Metastasis in Breast Cancer Patients}, volume = {59}, number = {8}, pages = {1212--1218}, year = {2018}, doi = {10.2967/jnumed.117.198846}, publisher = {Society of Nuclear Medicine}, 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{\textendash}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{\textendash}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{\textendash}2.94] vs. 2.29 [95\% CI, 2.00{\textendash}2.61; P \< 0.001] vs. 2.23 [95\% CI, 1.88{\textendash}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{\textendash}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.}, issn = {0161-5505}, URL = {https://jnm.snmjournals.org/content/59/8/1212}, eprint = {https://jnm.snmjournals.org/content/59/8/1212.full.pdf}, journal = {Journal of Nuclear Medicine} }