Metabolic Flare: Indicator of Hormone Responsiveness in Advanced Breast Cancer

2001 ◽  
Vol 19 (11) ◽  
pp. 2797-2803 ◽  
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.

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

2021 ◽  
Vol 17 (1) ◽  
pp. 20-26
Author(s):  
A.   V. Parnas ◽  
A.   I. Pronin ◽  
V.  S. Ilyakov ◽  
N.   A. Meshcheryakova ◽  
Z.  Kh. Kamolova ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Tissue ◽  
Imaging Modality ◽  
Receptor Expression ◽  
Breast Cancers ◽  
Positron Emission ◽  
Pet Ct ◽  
Er Positive ◽  
Er Expression

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.

scholarly journals 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

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.

In vitro evaluation of estrogenic, antiestrogenic and antitumor effects of amentoflavone

2021 ◽  
pp. 096032712199945
Author(s):  
AT Aliyev ◽  
S Ozcan-Sezer ◽  
A Akdemir ◽  
H Gurer-Orhan
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Antitumor Effects ◽  
Antiestrogenic Activity ◽  
Er Positive ◽  
In Vivo Effects ◽  
Mcf 7

Apigenin, a flavonoid, is reported to act as an estrogen receptor (ER) agonist and inhibit aromatase enzyme. However, amentoflavone, a biflavonoid bearing two apigenin molecules, has not been evaluated for its endocrine modulatory effects. Besides, it is highly consumed by young people to build muscles, enhance mood and lose weight. In the present study, apigenin was used as a reference molecule and ER mediated as well as ER-independent estrogenic/antiestrogenic activity of amentoflavone was investigated. Antitumor activity of amentoflavone was also investigated in both ER positive (MCF-7 BUS) and triple-negative (MDA-MB-231) breast cancer cells and its cytotoxicity was evaluated in human breast epithelial cells (MCF-10A). Our data confirmed ER agonist, aromatase inhibitory and cytotoxic effects of apigenin in breast cancer cells, where no ER mediated estrogenic effect and physiologically irrelevant, slight, aromatase inhibition was found for amentoflavone. Although selective cytotoxicity of amentoflavone was found in MCF-7 BUS cells, it does not seem to be an alternative to the present cytotoxic drugs. Therefore, neither an adverse effect, mediated by an estrogenic/antiestrogenic effect of amentoflavone nor a therapeutical benefit would be expected from amentoflavone. Further studies could be performed to investigate its in vivo effects.

scholarly journals Pulmonary Findings of [18F]FDG PET/CT Images on Asymptomatic COVID-19 Patients

Pathogens ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 839
Author(s):  
Tzu-Chuan Ho ◽  
Chin-Chuan Chang ◽  
Hung-Pin Chan ◽  
Ying-Fong Huang ◽  
Yi-Ming Arthur Chen ◽  
...  
Keyword(s):  
Systematic Review ◽  
Fdg Pet ◽  
Standardized Uptake Value ◽  
Fdg Uptake ◽  
Asymptomatic Patients ◽  
Positron Emission ◽  
Pet Ct ◽  
18F Fdg ◽  
Maximal Standardized Uptake Value ◽  
Fdg Pet Ct

During the coronavirus disease 2019 (COVID-19) pandemic, several case studies demonstrated that many asymptomatic patients with COVID-19 underwent fluorine-18 fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) examination for various indications. However, there is a lack of literature to characterize the pattern of [18F]FDG PET/CT imaging on asymptomatic COVID-19 patients. Therefore, a systematic review to analyze the pulmonary findings of [18F]FDG PET/CT on asymptomatic COVID-19 patients was conducted. This systematic review was performed under the guidelines of PRISMA. PubMed, Medline, and Web of Science were used to search for articles for this review. Articles with the key words: “asymptomatic”, “COVID-19”, “[18F]FDG PET/CT”, and “nuclear medicine” were searched for from 1 January 2020 to 20 May 2021. Thirty asymptomatic patients with COVID-19 were included in the eighteen articles. These patients had a mean age of 62.25 ± 14.85 years (male: 67.71 ± 12.00; female: 56.79 ± 15.81). [18F]FDG-avid lung lesions were found in 93.33% (28/30) of total patients. The major lesion was [18F]FDG-avid multiple ground-glass opacities (GGOs) in the peripheral or subpleural region in bilateral lungs, followed by the consolidation. The intensity of [18F]FDG uptake in multiple GGOs was 5.605 ± 2.914 (range from 2 to 12) for maximal standardized uptake value (SUVmax). [18F]FDG-avid thoracic lymph nodes (LN) were observed in 40% (12/40) of the patients. They mostly appeared in both mediastinal and hilar regions with an SUVmax of 5.8 ± 2.93 (range from 2.5 to 9.6). The [18F]FDG uptake was observed in multiple GGOs, as well as in the mediastinal and hilar LNs. These are common patterns in PET/CT of asymptomatic patients with COVID-19.

scholarly journals Coronary, aortic and carotid artery inflammation by 18F-fluorodeoxyglucose positron emission tomography in acute and chronic coronary artery disease

2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
W Nammas ◽  
S Uotila ◽  
J Teuho ◽  
M Pietila ◽  
J Airaksinen ◽  
...  
Keyword(s):  
Coronary Arteries ◽  
Fdg Pet ◽  
Carotid Arteries ◽  
Standardized Uptake Value ◽  
Chronic Coronary Artery Disease ◽  
Fdg Uptake ◽  
Positron Emission ◽  
Arterial Inflammation ◽  
18F Fdg ◽  
Artery Disease

Abstract Funding Acknowledgements Type of funding sources: None. Background 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) can detect arterial inflammation in individuals with atherosclerosis, but the associations among different vascular territories for 18F-FDG uptake are not known. Purpose We explored any possible correlation between arterial inflammation quantified by 18F-FDG PET in the aorta, carotid arteries, and coronary arteries in patients presenting with acute coronary syndrome (ACS), or chronic coronary artery disease (CAD). Methods Prospectively, we performed hybrid computed tomography angiography and 18F-FDG PET in 43 patients (26 ACS and 17 chronic CAD) at 6.6 ± 5.7 days following invasive coronary angiography. 18F-FDG PET was performed 90 minutes after injection of 302.2 ± 28.4 MBq 18F-FDG. Arterial 18F-FDG uptake was measured in the thoracic aorta, carotid arteries, and coronary arteries, and expressed as the target-to-background ratio (TBR; the ratio between arterial maximal standardized uptake value normalized to blood pool mean standardized uptake value) in the whole artery, and in the most diseased segment (MDS). Results Mean age was 64.9 ± 9.1 years, 90.7% males. The whole artery 18F-FDG uptake was higher in the aorta than in the carotid arteries (median TBR 2.23, interquartile range [0.36] vs. 1.88 [0.42], p < 0.001); whereas uptake in the coronary arteries was lower than in the aorta or carotid arteries (1.13 [0.23], p < 0.001 both). Similarly, 18F-FDG uptake in the aortic MDS was higher than in the carotid MDS (2.75 [0.62] vs. 2.25 [0.63], p < 0.001); whereas 18F-FDG uptake in the coronary MDS was the lowest (1.40 [0.33], p < 0.001 both). These findings were consistent in both ACS and chronic CAD patients. The whole artery 18F-FDG uptake of the aorta and carotid arteries correlated in patients with ACS (r = 0.58, p = 0.002), but not in patients with chronic CAD (r = 0.21, p = 0.3). There was no correlation between the whole artery 18F-FDG uptake in the coronary arteries and either the aorta or carotid arteries in the whole cohort (r=-0.16, p = 0.2, r = 0.01, p = 0.9, respectively), in patients with ACS (r = 0.06, p = 0.7, r=-0.01, p = 0.9, respectively), or in those with chronic CAD (r=-0.4, p = 0.1, r=-0.09, p = 0.7, respectively). Conclusions In patients with ACS or chronic CAD, large arteries had higher 18F-FDG uptake than the coronary arteries. The intensity of 18F-FDG uptake in the coronary arteries did not correlate with that in the carotid arteries or the aorta, indicating that disease activity differs between large arteries and coronary arteries.

scholarly journals FAPI-PET/CT: A New Direction For Diagnostic Imaging In Nuclear Medicine

2019 ◽  
pp. 48-54
Author(s):  
Pavel Korol ◽  
A. Samokhin ◽  
Oleg Shcherbina
Keyword(s):  
Breast Cancer ◽  
Standardized Uptake Value ◽  
Emission Tomography ◽  
Tumor Diseases ◽  
Positron Emission ◽  
Pet Ct ◽  
Routine Medical Practice ◽  
Technological Improvements ◽  
High Absorption ◽  
Prospects Of Application

The literature review addresses the prospects of application, FAPI-PET / CT, as a new method for diagnostic visualization of malignant tumor diseases. According to the study, a number of epidemiologically important tumor diseases, in particular breast cancer, esophagus, lungs, pancreas, tumors of the head and neck, colorectal cancer, have an extremely high absorption of FAPI in the execution of 68-Ga-FAPI-PET / CT. However, further technological improvements are required in order for FAPI-PET / CT imaging, by computing SUV, to become part of routine medical practice. Key words: positron emission tomography, radiopharmaceutical, fibroblast-associated protein, standardized uptake value.

scholarly journals Overexpression of BQ323636.1 Modulated AR/IL-8/CXCR1 Axis to Confer Tamoxifen Resistance in ER-Positive Breast Cancer

Life ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 93
Author(s):  
Ho Tsoi ◽  
Ling Shi ◽  
Man-Hong Leung ◽  
Ellen P. S. Man ◽  
Zi-Qing So ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Tamoxifen Resistance ◽  
In Silico Analysis ◽  
Luciferase Reporter ◽  
Androgen Response Element ◽  
Er Positive

NCOR2 is a co-repressor for estrogen receptor (ER) and androgen receptor (AR). Our group previously identified a novel splice variant of NCOR2, BQ323636.1 (BQ), that mediates tamoxifen resistance via interference of NCOR2 repression on ER. Luciferase reporter assay showed BQ overexpression could enhance the transcriptional activity of androgen response element (ARE). We proposed that BQ employs both AR and ER to confer tamoxifen resistance. Through in silico analysis, we identified interleukin-8 (IL-8) as the sole ERE and ARE containing gene responsiveness to ER and AR activation. We confirmed that BQ overexpression enhanced the expression of IL-8 in ER+ve breast cancer cells, and AR inhibition reduced IL-8 expression in the BQ overexpressing cell lines, suggesting that AR was involved in the modulation of IL-8 expression by BQ. Moreover, we demonstrated that IL-8 could activate both AKT and ERK1/2 via CXCR1 to confer tamoxifen resistance. Targeting CXCR1/2 by a small inhibitor repertaxin reversed tamoxifen resistance of BQ overexpressing breast cancer cells in vitro and in vivo. In conclusion, BQ overexpression in ER+ve breast cancer can enhance IL-8 mediated signaling to modulate tamoxifen resistance. Targeting IL-8 signaling is a promising approach to overcome tamoxifen resistance in ER+ve breast cancer.

scholarly journals HOXA5 Expression Is Elevated in Breast Cancer and Is Transcriptionally Regulated by Estradiol

2020 ◽  
Vol 11 ◽  
Author(s):  
Imran Hussain ◽  
Paromita Deb ◽  
Avisankar Chini ◽  
Monira Obaid ◽  
Arunoday Bhan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Female Rats ◽  
Er Positive ◽  
Gene Regulatory ◽  
Cancer Tissues ◽  
Positive Breast Cancer

HOXA5 is a homeobox-containing gene associated with the development of the lung, gastrointestinal tract, and vertebrae. Here, we investigate potential roles and the gene regulatory mechanism in HOXA5 in breast cancer cells. Our studies demonstrate that HOXA5 expression is elevated in breast cancer tissues and in estrogen receptor (ER)-positive breast cancer cells. HOXA5 expression is critical for breast cancer cell viability. Biochemical studies show that estradiol (E2) regulates HOXA5 gene expression in cultured breast cancer cells in vitro. HOXA5 expression is also upregulated in vivo in the mammary tissues of ovariectomized female rats. E2-induced HOXA5 expression is coordinated by ERs. Knockdown of either ERα or ERβ downregulated E2-induced HOXA5 expression. Additionally, ER co-regulators, including CBP/p300 (histone acetylases) and MLL-histone methylases (MLL2, MLL3), histone acetylation-, and H3K4 trimethylation levels are enriched at the HOXA5 promoter in present E2. In summary, our studies demonstrate that HOXA5 is overexpressed in breast cancer and is transcriptionally regulated via estradiol in breast cancer cells.

scholarly journals Correlation Between 18F-FDG Uptake and Immune Cell Infiltration in Metastatic Brain Lesions

2021 ◽  
Vol 11 ◽  
Author(s):  
Young-Sil An ◽  
Se-Hyuk Kim ◽  
Tae Hoon Roh ◽  
So Hyun Park ◽  
Tae-Gyu Kim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Cells ◽  
Immune Cell ◽  
Standardized Uptake Value ◽  
Brain Lesions ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Ki 67 ◽  
Glucose Transporter 1 ◽  
Fdg Uptake

BackgroundThe purpose of this study was to investigate the correlation between 18F-fluorodeoxyglucose (FDG) uptake and infiltrating immune cells in metastatic brain lesions.MethodsThis retrospective study included 34 patients with metastatic brain lesions who underwent brain 18F-FDG positron emission tomography (PET)/computed tomography (CT) followed by surgery. 18F-FDG uptake ratio was calculated by dividing the standardized uptake value (SUV) of the metastatic brain lesion by the contralateral normal white matter uptake value. We investigated the clinicopathological characteristics of the patients and analyzed the correlation between 18F-FDG uptake and infiltration of various immune cells. In addition, we evaluated immune-expression levels of glucose transporter 1 (GLUT1), hexokinase 2 (HK2), and Ki-67 in metastatic brain lesions.ResultsThe degree of 18F-FDG uptake of metastatic brain lesions was not significantly correlated with clinical parameters. There was no significant relationship between the 18F-FDG uptake and degree of immune cell infiltration in brain metastasis. Furthermore, other markers, such as GLUT1, HK2, and Ki-67, were not correlated with degree of 18F-FDG uptake. In metastatic brain lesions that originated from breast cancer, a higher degree of 18F-FDG uptake was observed in those with high expression of CD68.ConclusionsIn metastatic brain lesions, the degree of 18F-FDG uptake was not significantly associated with infiltration of immune cells. The 18F-FDG uptake of metastatic brain lesions from breast cancer, however, might be associated with macrophage activity.

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