Analyzing the Estrogen Receptor Status of Liver Metastases with [18F]-FES-PET in Patients with Breast Cancer

Abstract

Background: Positron emission tomography (PET) with 16α-[18F]-fluoro-17β-estradiol ([18F]-FES) can visualize estrogen receptor (ER) expression, but it is challenging to determine the ER status of liver metastases, due to high physiological [18F]-FES uptake. We evaluated whether [18F]-FES-PET can be used to determine the ER status of liver metastases, using corresponding liver biopsies as the gold standard. Methods: Patients with metastatic breast cancer (n = 23) were included if they had undergone a [18F]-FES-PET, liver metastasis biopsy, CT-scan, and [18F]-FDG-PET. [18F]-FES-PET scans were assessed by visual and quantitative analysis, tracer uptake was correlated with ER expression measured by immunohistochemical staining and the effects of region-of-interest size and background correction were determined. Results: Visual analysis allowed ER assessment of liver metastases with 100% specificity and 18% sensitivity. Quantitative analysis improved the sensitivity. Reduction of the region-of-interest size did not further improve the results, but background correction improved ER assessment, resulting in 83% specificity and 77% sensitivity. Using separate thresholds for ER+ and ER− metastases, positive and negative predictive values of 100% and 75%, respectively, could be obtained, although 30% of metastases remained inconclusive. Conclusion: In the majority of liver metastases, ER status can be determined with [18F]-FES-PET if background correction and separate thresholds are applied.

Molecular Imaging of Steroid Receptors in Breast Cancer

“…FES demonstrates rapid uptake in the liver in keeping with usual steroid metabolism 80,81 . Hepatic uptake significantly limits evaluation of ER-positive metastases in the liver 40,81,82 . FES is then excreted into the biliary system and enters into the small bowel with little activity observed in the colon due to reabsorption and renal excretion 80,81 .…”

“…Another limitation is the potential for false-negative and false-positive results, which are important to consider during FES PET interpretation. False-negatives can occur in lesions with low levels of ER expression, lesions in the liver or small bowel, or peritoneal carcinomatosis due to high physiologic clearance, with pleural effusions and ascites, with lesions that are small size (typically less than 1 cm) due to partial volume effects, and with pharmacological treatment with ER-binding medications as discussed above 40,57,82,83,95,96 . False-positive findings have been reported with radiation fibrosis/pneumonitis, fibrous dysplasia, insufficiency fractures, meningiomas, and uterine leiomyomas 29,96–103 .…”

“…80,81 Hepatic uptake significantly limits evaluation of ER-positive metastases in the liver. 40,81,82 FES is then excreted into the biliary system and enters into the small bowel with little activity observed in the colon due to reabsorption and renal excretion. 80,81 The patient receives approximately 0.022 mSv/MBq (80 mrem/mCi) effective dose equivalent with the liver receiving the highest dose (0.13 mGy/ MBq, 380 mrad/mCi), followed by the gallbladder and urinary bladder.…”

“…False-negatives can occur in lesions with low levels of ER expression, lesions in the liver or small bowel, or peritoneal carcinomatosis due to high physiologic clearance, with pleural effusions and ascites, with lesions that are small size (typically less than 1 cm) due to partial volume effects, and with pharmacological treatment with ER-binding medications as discussed above. 40,57,82,83,95,96 False-positive findings have been reported with radiation fibrosis/pneumonitis, fibrous dysplasia, insufficiency fractures, meningiomas, and uterine leiomyomas. 29,[96][97][98][99][100][101][102][103] Despite these limitations, FES PET is a powerful new tool for patients with advanced ER-positive breast cancer.…”

Dynamic whole-body [18F]FES PET/CT increases lesion visibility in patients with metastatic breast cancer

“…However, a major limitation of the [ 18 F]FES radiotracer is the metabolism, excretion, and thereby high physiological uptake in the liver. This can result in undetectable metastases, cold spots, or heterogeneous uptake corresponding to the location of liver metastases[ 24 , 31 ]. In a study of 91 patients scanned using [ 18 F]FES, no liver lesions or lesions directly adjacent to the liver were detectable because of physiological radiotracer uptake in the liver [ 15 ].…”