Quantitative FES-PET can predict response to hormonal therapy and may help guide treatment selection. Treatment selection using quantitative FES-PET in our patient series would have increased the rate of response from 23% to 34% overall, and from 29% to 46% in the subset of patients lacking HER2/neu overexpression. A multi-institutional collaborative trial would permit definitive assessment of the value of FES-PET for therapeutic decision making.
The PET compound 18 F-fluoroestradiol ( 18 F-FES) has been developed and tested as an agent for the imaging of estrogen receptor (ER) expression in vivo. 18 F-FES uptake has been shown to correlate with ER expression assayed in vitro by radioligand binding; however, immunohistochemistry (IHC) rather than radioligand binding is used most often to measure ER expression in clinical practice. We therefore compared 18 F-FES uptake with ER expression assayed in vitro by IHC with both qualitative and semiquantitative measures. Methods: Seventeen patients with primary or metastatic breast cancer were studied with dynamic 18 F-FES PET; cancer tissue samples, collected close to the time of imaging, were assayed for ER expression by IHC. For each tumor, partial-volume-corrected measures of 18 F-FES uptake were compared with ER expression measured by 3 different ER scoring methods: qualitative scoring (0-31), the Allred score (0-10), and a computerized IHC index. Results: There was excellent agreement (r 5 0.99) between observers using IHC as well as the different methods of measuring ER content (P , 0.001). ER-negative tumors had 18 F-FES partial-volumecorrected standardized uptake values of less than 1.0, whereas ER-positive tumors had values above 1.1. Correlation coefficients for the different measures of ER content and the different measures of 18 F-FES uptake ranged from 0.57 to 0.73, with the best correlation being between the computerized IHC index and 18 F-FES partial-volume-corrected standardized uptake values. Conclusion: Our results showed good agreement between 18 F-FES PET and ER expression measured by IHC. 18 F-FES imaging may be a useful tool for aiding in the assessment of ER status, especially in patients with multiple tumors or for tumors that are difficult to biopsy.
Introduction
18F-Fluoroestradiol (FES) PET imaging provides a non-invasive method to measure estrogen receptor (ER) expression in tumors. Assessment of factors that could affect the quantitative level of FES uptake is important as part of the validation of FES PET for evaluating regional ER expression in breast cancer.
Methods
This study examines FES uptake in tumors from 312 FES PET scans (239 patients) with documented ER+ primary breast cancer. FES uptake was compared to clinical and laboratory data; treatment prior to or at time of scan; and properties of FES and its metabolism and transport. Linear mixed models were used to explore univariate, threshold-based, and multivariate associations.
Results
Sex-hormone binding globulin (SHBG) was inversely associated with FES SUV. Average FES uptake did not differ by levels of plasma estradiol, age, or rate of FES metabolism. FES tumor uptake was greater for patients with a higher body mass index (BMI), but this effect did not persist when SUV was corrected for lean body mass (LBM). In multivariate analysis, only plasma SHBG binding was an independent predictor of LBM-adjusted FES SUV.
Conclusions
Calculation of FES SUV, possibly adjusted for lean body mass, should be sufficient to assess FES uptake for the purpose of inferring ER expression. Pre-menopausal estradiol levels do not appear to interfere with FES uptake. The availability and binding properties of SHBG influence FES uptake and should be measured. Specific activity did not have a clear influence on FES uptake, except perhaps at higher injected mass/kg. These results suggest that FES imaging protocols may be simplified without sacrificing the validity of the results.
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