[18F]-Fluoroestradiol PET/CT: a modern look at nuclear medicine applications

Breast cancer is one of the most commonly diagnosed cancers and the leading cause of cancer mortality among women. Approximately 70–80 % of breast cancers are estrogen (ER) and/or progesterone receptor-positive, thus making endocrine therapy an important stage of treatment. Receptor expression in breast cancer cells is usually assessed by tissue immunohistochemistry. The method of positron emission tomography, combined with computed tomography (PET/CT), makes it possible to evaluate not only anatomical and structural, but also metabolic changes in tumor tissue. 18F-Fluoroestradiol (18F-FES) is a radiopharmaceutical drug, an estradiol analogue, which is used in the diagnostics of ER-expressing tumors and is utilized for detection and quantification of ER expression in vivo. Various studies show that 18F-FES accumulation indicates presence of ER-positive tumor tissue, which, in most cases, is confirmed by tissue immunohistochemistry. Although current guidelines recommend 18F-fluorodeoxyglucose PET/CT when routine examinations demonstrate ambiguous results, 18F-FES PET/CT can be the preferable imaging modality in the diagnostics of ER-positive breast cancer. It should be noted, that PET/CT with 18F-FES can also be effective for evaluation of tumors with a high level of ER expression, like ovarian cancer.

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Monitoring the Early Response of Fulvestrant Plus Tanshinone IIA Combination Therapy to Estrogen Receptor-Positive Breast Cancer by Longitudinal 18F-FES PET/CT

Contrast Media & Molecular Imaging ◽

10.1155/2019/2374565 ◽

2019 ◽

Vol 2019 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

SiMin He ◽

MingWei Wang ◽

YongPing Zhang ◽

JianMin Luo ◽

YingJian Zhang

Keyword(s):

Combination Therapy ◽

Ex Vivo ◽

Early Response ◽

Ct Imaging ◽

Tanshinone Iia ◽

Breast Cancers ◽

Antitumor Effects ◽

Pet Ct ◽

Er Positive

Endocrine monotherapy of breast cancers is generally hampered by the primary/acquired resistance and adverse sides in clinical settings. Herein, advantaging the multitargeting antitumor effects and normal organ-protecting roles of Chinese herbal medicine, the aim of this study was to investigate the enhanced synergistic efficacy of fulvestrant plus Tan IIA combination therapy in ER-positive breast cancers and to monitor the early response by longitudinal 18F-FES PET/CT imaging. The experimental results showed FUL + Tan IIA combination therapy significantly inhibited tumor growth of ER-positive ZR-75-1 tumor xenografts and exhibited distinct antitumor effects at an earlier time point after treatment than did the monotherapy of FUL or Tan IIA. Moreover, 18F-FES PET/CT imaging competently monitored the early response of FUL + Tan IIA combination therapy. The quantitative 18F-FES %ID/gmax in vivo was further confirmed by and correlated well with ERα expression ex vivo. In conclusion, the synergic effect of FUL + Tan IIA combination therapy to ER-positive breast cancers was verified in the preclinical tumor models and the early treatment response could be monitored by 18F-FES PET/CT.

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Estrogen deprivation triggers an immunosuppressive phenotype in breast cancer cells

10.1101/715136 ◽

2019 ◽

Cited By ~ 3

Author(s):

Daniela Hühn ◽

Pablo Martí-Rodrigo ◽

Silvana Mouron ◽

Catherine S. Hansel ◽

Kirsten Tschapalda ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Breast Cancers ◽

Breast Cancer Patients ◽

Mcf7 Cells ◽

Estrogen Deprivation ◽

Er Positive

ABSTRACTEstrogen receptor (ER)-positive breast tumors are routinely treated with estrogen-depriving therapies. Despite their effectiveness, patients often progress into a more aggressive form of the disease. Through a chemical screen oriented to identify chemicals capable of inducing the expression of the immune-checkpoint ligand PD-L1, we found antiestrogens as hits. Subsequent validations confirmed that estrogen deprivation or ERα depletion induces PD-L1 expression in ER-positive breast cancer cells, both in vitro and in vivo. Likewise, PD-L1 expression is increased in metastasis arising from breast cancer patients receiving adjuvant hormonal therapy for their local disease. Transcriptome analyses indicate that estrogen deprivation triggers a broad immunosuppressive program, not restricted to PD-L1. Accordingly, estrogen deprived MCF7 cells are resistant to T-cell mediated cell killing, in a manner that can be reverted by estradiol. Our study reveals that while antiestrogen therapies effectively limit tumor growth in ER-positive breast cancers, they also trigger a transcriptional program that favors immune evasion.

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Androgen Receptor Expression Associates With Distinctive Clinicopathological and Molecular Features in ER-Positive and ER-Negative Breast Cancer

10.21203/rs.3.rs-958949/v2 ◽

2021 ◽

Author(s):

Taobo Hu ◽

Yiqiang Liu ◽

Guiyang Zhao ◽

Shu Wang ◽

Mengping Long

Keyword(s):

Breast Cancer ◽

Androgen Receptor ◽

Clinicopathological Characteristics ◽

Receptor Expression ◽

Molecular Features ◽

Molecular Correlation ◽

Er Positive ◽

Er Expression ◽

Positive Breast Cancer

Abstract Background: Androgen receptor (AR) expression is frequently observed in breast cancer, but its association with estrogen receptor (ER) expression of breast cancer remains unclear. Methods: In this study, we analyzed the clinicopathological and molecular features associated AR loss in ER-positive and ER-negative breast cancer respectively, trying to elucidate the molecular correlation between AR and ER. Results: Our results showed that AR loss was associated with different clinicopathological characteristics in ER-positive and ER-negative breast cancer. Moreover, the expression of AR was correlated with different molecular features in ER-positive and ER-negative breast cancer.Conclusions: These results suggest that the role of AR in ER-positive breast cancer is distinctive from that in ER-negative breast cancer.

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One-Step 18F-Labeling of Estradiol Derivative for PET Imaging of Breast Cancer

Contrast Media & Molecular Imaging ◽

10.1155/2018/5362329 ◽

2018 ◽

Vol 2018 ◽

pp. 1-9

Author(s):

Hongbo Huang ◽

Ke Li ◽

Gaochao Lv ◽

Guiqing Liu ◽

Xueyu Zhao ◽

...

Keyword(s):

Breast Cancer ◽

Pet Imaging ◽

Cell Uptake ◽

Breast Cancer Cell Lines ◽

Breast Cancers ◽

Isotope Exchange Reaction ◽

Er Positive ◽

One Step ◽

Mcf 7

Positron emission tomography (PET) imaging is a useful method to evaluate in situ estrogen receptor (ER) status for the early diagnosis of breast cancer and optimization of the appropriate treatment strategy. The 18F-labeled estradiol derivative has been successfully used to clinically assess the ER level of breast cancer. In order to simplify the radiosynthesis process, one-step 18F-19F isotope exchange reaction was employed for the 18F-fluorination of the tracer of [18F]AmBF3-TEG-ES. The radiotracer was obtained with the radiochemical yield (RCY) of ~61% and the radiochemical purity (RCP) of >98% within 40 min. Cell uptake and blocking assays indicated that the tracer could selectively accumulate in the ER-positive human breast cancer cell lines MCF-7 and T47D. In vivo PET imaging on the MCF-7 tumor-bearing mice showed relatively high tumor uptake (1.4~2.3 %D/g) and tumor/muscle uptake ratio (4~6). These results indicated that the tracer is a promising PET imaging agent for ER-positive breast cancers.

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Androgen Receptor Expression Associates With Distinctive Clinicopathological and Molecular Features in ER-Positive and ER-Negative Breast Cancer

10.21203/rs.3.rs-958949/v1 ◽

2021 ◽

Author(s):

Taobo Hu ◽

Yiqiang Liu ◽

Guiyang Zhao ◽

Shu Wang ◽

Mengping Long

Keyword(s):

Breast Cancer ◽

Androgen Receptor ◽

Clinicopathological Characteristics ◽

Receptor Expression ◽

Molecular Features ◽

Molecular Correlation ◽

Er Positive ◽

Er Expression ◽

Positive Breast Cancer

Abstract Background Androgen receptor (AR) expression is frequently observed in breast cancer, but its association with estrogen receptor (ER) expression of breast cancer remains unclear. Methods In this study, we analyzed the clinicopathological and molecular features associated AR loss in ER-positive and ER-negative breast cancer respectively, trying to elucidate the molecular correlation between AR and ER. Results Our results showed that AR loss was associated with different clinicopathological characteristics in ER-positive and ER-negative breast cancer. Moreover, the expression of AR was correlated with different molecular features in ER-positive and ER-negative breast cancer. Conclusions These results suggest that the role of AR in ER-positive breast cancer is distinctive from that in ER-negative breast cancer.

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Metabolic Flare: Indicator of Hormone Responsiveness in Advanced Breast Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2001.19.11.2797 ◽

2001 ◽

Vol 19 (11) ◽

pp. 2797-2803 ◽

Cited By ~ 254

Author(s):

Joanne E. Mortimer ◽

Farrokh Dehdashti ◽

Barry A. Siegel ◽

Kathryn Trinkaus ◽

John A. Katzenellenbogen ◽

...

Keyword(s):

Breast Cancer ◽

Standardized Uptake Value ◽

Tamoxifen Therapy ◽

Fdg Uptake ◽

Percentage Decrease ◽

Positron Emission ◽

Before And After ◽

Er Positive ◽

Induced Changes

PURPOSE: The purpose of this study was to investigate whether positron emission tomography (PET) with the glucose analog [18F]fluorodeoxyglucose (FDG) and the estrogen analog 16 alpha-[18F]fluoroestradiol-17 beta (FES), performed before and after treatment with tamoxifen, could be used to detect hormone-induced changes in tumor metabolism (metabolic flare) and changes in available levels of estrogen receptor (ER). In addition, we investigated whether these PET findings would predict hormonally responsive breast cancer. PATIENTS AND METHODS: Forty women with biopsy-proved advanced ER-positive (ER+) breast cancer underwent PET with FDG and FES before and 7 to 10 days after initiation of tamoxifen therapy; 70 lesions were evaluated. Tumor FDG and FES uptake were assessed semiquantitatively by the standardized uptake value (SUV) method. The PET results were correlated with response to hormonal therapy. RESULTS: In the responders, the tumor FDG uptake increased after tamoxifen by 28.4% ± 23.3% (mean ± SD); only five of these patients had evidence of a clinical flare reaction. In nonresponders, there was no significant change in tumor FDG uptake from baseline (mean change, 10.1% ± 16.2%; P = .0002 v responders). Lesions of responders had higher baseline FES uptake (SUV, 4.3 ± 2.4) than those of nonresponders (SUV, 1.8 ± 1.3; P = .0007). All patients had evidence of blockade of the tumor ERs 7 to 10 days after initiation of tamoxifen therapy; however, the degree of ER blockade was greater in the responders (mean percentage decrease, 54.8% ± 14.2%) than in the nonresponders (mean percentage decrease, 19.4% ± 17.3%; P = .0003). CONCLUSION: The functional status of tumor ERs can be characterized in vivo by PET with FDG and FES. The results of PET are predictive of responsiveness to tamoxifen therapy in patients with advanced ER+ breast cancer.

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Comparison of diagnostic accuracy of 18F-fluoroestradiol and 18F-fluorodeoxyglucose positron emission tomography/computed tomography for breast cancer recurrence in patients with a history of estrogen receptor-positive primary breast cancer

10.21203/rs.3.rs-18613/v1 ◽

2020 ◽

Author(s):

Sun Young Chae ◽

Hye Joo Son ◽

Dong Yun Lee ◽

Eonwoo Shin ◽

Jungsu S. Oh ◽

...

Keyword(s):

Breast Cancer ◽

Diagnostic Accuracy ◽

Fdg Pet ◽

Primary Breast Cancer ◽

Cancer Recurrence ◽

Positron Emission ◽

Pet Ct ◽

Er Positive ◽

18F Fdg ◽

Fdg Pet Ct

Abstract Background To compare the diagnostic accuracy of 18F-fluoroestradiol (18F-FES) and 18F-fluorodoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) for breast cancer recurrence in patients with estrogen receptor (ER)-positive primary breast cancer.Methods Our database of consecutive patients enrolled in a previous prospective cohort study to assess 18F-FES PET/CT was reviewed to identify eligible patients who had ER-positive primary breast cancer with suspected first recurrence at presentation and who underwent 18F-FDG PET/CT. The diagnostic accuracy of qualitative 18F-FES and 18F-FDG PET/CT interpretations was assessed, comparing them with histological diagnoses.Results Of the 46 enrolled patients, 45 were confirmed as having recurrent breast cancer, while one was diagnosed with chronic granulomatous inflammation. Forty (89%) patients were ER-positive, four (9%) were ER-negative, and one (2%) patient did not undergo an ER assay. The sensitivity of 18F-FES PET/CT was 71.1% (32/45, 95% CI: 55.7–83.6), while that of 18F-FDG PET/CT was 80.0% (36/45, 95% CI: 65.4–90.4) when malignant interpretation was defined as positive, and 93.3% (42/45, 95% CI: 81.7–98.6) when an equivocal or malignant interpretation was considered positive. There was no significant difference in sensitivity between 18F-FES and 18F-FDG PET/CT (P=0.48) when malignant 18F-FDG interpretation was considered positive, but the sensitivity of 18F-FDG was significantly higher than 18F-FES (P=0.013) when equivocal or malignant interpretation was considered positive. One patient with a benign lesion showed negative 18F-FES but malignant 18F-FDG uptake.Conclusions The restaging of patients who had ER-positive primary breast cancer and present with recurrent disease may include 18F-FES PET/CT.

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FGFR1 Is Associated With Tamoxifen Resistance and Poor Prognosis of ER-Positive Breast Cancers by Suppressing ER Protein Expression

Technology in Cancer Research & Treatment ◽

10.1177/15330338211004935 ◽

2021 ◽

Vol 20 ◽

pp. 153303382110049

Author(s):

Qing Lv ◽

Shiming Guan ◽

Mingjie Zhu ◽

Hu Huang ◽

Junqiang Wu ◽

...

Keyword(s):

Breast Cancer ◽

Protein Expression ◽

Cox Regression ◽

Breast Cancer Prognosis ◽

Cancer Prognosis ◽

In Vitro Assays ◽

Breast Cancers ◽

Er Positive ◽

Fgfr1 Expression ◽

Er Expression

Fibroblast growth factor receptor 1 (FGFR1) is widely recognized as a key player in mammary carcinogenesis and associated with the prognosis and therapeutic response of breast cancers. With the aim of investigating the correlation between FGFR1 expression and estrogen receptor (ER) and exploring the effect of FGFR1 on endocrine therapy response and ER+ breast cancer prognosis, we examined the FGFR1 protein expression among 184 ER-positive breast cancers by the immunohistochemistry (IHC) method, analyzed the association between FGFR1 expression and disease characters using the Pearson’s chi-square test, and assessed the prognostic role of FGFR1 among breast cancers using Cox regression and Kaplan-Meier analyses. Moreover, in vitro assays were conducted to confirm the correlation between FGFR1 and ER expression and investigate the effect of FGFR1 on tamoxifen (TAM) sensitivity in ER+ breast cancer. The results showed that ER expression was negatively correlated with FGFR1 expression ( P = 0.011, r = -0.221). Moreover, FGFR1 expression was one of the prognostic factors of ER-positive breast cancer (OR = 1.974, 95% CI = 1.043-3.633), and high FGFR1 expression was correlated with decreased breast cancer overall survival. In addition, knocking down FGFR1 inhibited cell proliferation and enhanced TAM sensitivity in TAM-resistant cells. In conclusion, we found that there was a significant negative correlation between FGFR1 and ER levels in ER+ breast cancers, high FGFR1 protein expression was associated with poor breast cancer prognosis, down-regulating FGFR1 could elevate ER expression and is associated with enhanced TAM sensitivity in ER+ breast cancers.

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Comparison of diagnostic sensitivity of 18F-fluoroestradiol and 18F-fluorodeoxyglucose positron emission tomography/computed tomography for breast cancer recurrence in patients with a history of estrogen receptor-positive primary breast cancer

10.21203/rs.3.rs-18613/v2 ◽

2020 ◽

Author(s):

Sun Young Chae ◽

Hye Joo Son ◽

Dong Yun Lee ◽

Eonwoo Shin ◽

Jungsu S. Oh ◽

...

Keyword(s):

Breast Cancer ◽

Fdg Pet ◽

Primary Breast Cancer ◽

Cancer Recurrence ◽

Emission Tomography ◽

Fdg Uptake ◽

Positron Emission ◽

Pet Ct ◽

Er Positive ◽

Fdg Pet Ct

Abstract Background To compare the diagnostic sensitivity of [ 18 F]fluoroestradiol ([ 18 F]FES) and [ 18 F]fluorodeoxyglucose ([ 18 F]FDG) positron emission tomography/computed tomography (PET/CT) for breast cancer recurrence in patients with estrogen receptor (ER)-positive primary breast cancer. Methods Our database of consecutive patients enrolled in a previous prospective cohort study to assess [ 18 F]FES PET/CT was reviewed to identify eligible patients who had ER-positive primary breast cancer with suspected first recurrence at presentation and who underwent [ 18 F]FDG PET/CT. The sensitivity of qualitative [ 18 F]FES and [ 18 F]FDG PET/CT interpretations was assessed, comparing them with histological diagnoses. Results Of the 46 enrolled patients, 45 were confirmed as having recurrent breast cancer, while one was diagnosed with chronic granulomatous inflammation. Forty (89%) patients were ER-positive, four (9%) were ER-negative, and one (2%) patient did not undergo an ER assay. The sensitivity of [ 18 F]FES PET/CT was 71.1% (32/45, 95% CI: 55.7–83.6), while that of [ 18 F]FDG PET/CT was 80.0% (36/45, 95% CI: 65.4–90.4) with a threshold of positive interpretation, and 93.3% (42/45, 95% CI: 81.7–98.6) when a threshold of equivocal was used. There was no significant difference in sensitivity between [ 18 F]FES and [ 18 F]FDG PET/CT ( P =0.48) with a threshold of positive [ 18 F]FDG uptake, but the sensitivity of [ 18 F]FDG was significantly higher than [ 18 F]FES ( P =0.013) with a threshold of equivocal [ 18 F]FDG uptake. One patient with a benign lesion showed negative [ 18 F]FES but positive [ 18 F]FDG uptake. Conclusions The restaging of patients who had ER-positive primary breast cancer and present with recurrent disease may include [ 18 F]FES PET/CT as an initial test when standard imaging studies are equivocal or suspicious.

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