Recommendations and Technical Aspects of 16α-[18F]Fluoro-17β-Estradiol PET to Image the Estrogen Receptor In Vivo

Venema, Clasina M; Apollonio, Giulia; Hospers, Geke A.P.; Schröder, Carolina P.; Dierckx, Rudi; Vries, Erik F. J. de; Glaudemans, Andor W J M

doi:10.1097/rlu.0000000000001347

Cited by 43 publications

(108 citation statements)

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“…Many studies have evaluated 18 F-FES PET imaging as a method for quantifying ER expression, predicting response to therapy, and optimizing doses of ER blocking agents (8)(9)(10)(11)(12)(13)(14)(15). Their results provide the rationale for an ongoing multi-institutional validation trial in the United States and increasing clinical use in Europe of 18 F-FES PET as an additional diagnostic tool when conventional imaging is inconclusive (21,22). Given the prevalence of ESR1 mutations in metastatic breast cancer, it is plausible that ESR1 mutations may contribute to the reported diversity between 18 F-FES uptake both within and among patients (23)(24)(25) and could result in a false-negative PET imaging result if these mutations impair 18 F-FES binding.…”

Section: Discussionmentioning

confidence: 99%

¹⁸F-Fluoroestradiol PET Imaging of Activating Estrogen Receptor-α Mutations in Breast Cancer

et al. 2019

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The purpose of this study was to determine the effect of estrogen receptor-α gene (ESR1) mutations at the tyrosine (Y) 537 amino acid residue within the ligand binding domain on 18 F-fluoroestradiol ( 18 F-FES) binding and in vivo tumor uptake compared with wild-type (WT)-estrogen receptor α (ER). Methods: ER-negative MDA-MB-231 breast cancer cells were used to generate stable cell lines that express WT-ER, Y537S, or Y537C mutant ER. Receptor expression and localization were confirmed by Western blot and immunofluorescence, respectively. ER transcriptional function was measured using an estrogen response element-luciferase reporter gene assay and quantitative polymerase chain reaction analysis of ER-regulated endogenous target genes. Saturation binding and competition assays were performed to determine equilibrium dissociation constant (K d ) and half maximal inhibitory concentration (IC50) values. 18 F-FES uptake was measured in tumor xenografts grown in female athymic nude mice by small-animal PET/CT imaging and tissue biodistribution using 5.55 MBq (150 μCi) of 18 F-FES. A 10-fold-lower injected dose of 0.555 MBq (15 μCi) of 18 F-FES was also used for tissue biodistribution. Statistical significance was determined using ANOVA. Results: Y537S and Y537C mutations resulted in increased ER transcriptional activity in the absence of estrogen compared with WT-ER (11.48 ± 2.42 fold; P 5 0.0002, and 5.89 ± 0.94 fold; P 5 0.04, respectively). Constitutive ER activation of two target genes (PGR and TFF1) in the absence of estrogen was also observed in Y537S-and Y537C-ER cells compared with WT-ER. K d values for 18 F-FES were 0.98 ± 0.54 nM for Y537S-ER (P 5 0.27) and 0.24 ± 0.03 nM for Y537C-ER (P 5 0.95) compared with 0.07 ± 0.03 nM for WT-ER. IC50 values were 0.22 ± 0.09 nM for Y537S-ER (P 5 0.97), 0.18 ± 0.09 nM for Y537C-ER (P 5 0.99), and 0.19 ± 0.11 nM for WT-ER. Tumor xenografts expressing Y537S-ER (mean percentage injected dose per gram, 1.45 ± 0.06; P 5 0.77) and Y537C-ER (2.09 ± 0.20; P 5 0.21) had similar 18 F-FES uptake compared with WT-ER (1.68 ± 0.12). Comparable 18 F-FES uptake between Y537S-, Y537C-, and WT-ER xenografts was also observed using a 10-fold-lower injected dose with the tissue biodistribution assay. Conclusion: Since tumoral uptake of 18 F-FES is not significantly impacted by Y537S-ER or Y537C-ER mutations, the potential diagnostic utility of 18 F-FES PET imaging is expected to be equally valid for patients with or without these activating ESR1 mutations.

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Section: Discussionmentioning

confidence: 99%

¹⁸F-Fluoroestradiol PET Imaging of Activating Estrogen Receptor-α Mutations in Breast Cancer

et al. 2019

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“…We performed a prospective, 2-center feasibility trial (NCT01988324). The primary endpoint was the concordance of 18 F-FDHT and 18 F-FES uptake with, respectively, AR and ER expression in a newly obtained biopsy of a metastasis measured by immunohistochemistry. Secondary endpoints were the optimum threshold to discriminate positive and negative lesions for both AR and ER on PET, inter-and intrapatient 18 F-FDHT and 18 F-FES heterogeneity, and correlation between tracer uptake and serum hormone levels at the time of scanning.…”

Section: Methodsmentioning

confidence: 99%

“…Molecular imaging offers the possibility to noninvasively determine the presence of relevant drug targets in all metastases within an individual patient. Tumor ER expression can be visualized by 18 F-fluoroestradiol ( 18 F-FES) PET in breast cancer patients (9). AR expression in prostate cancer patients has been evaluated using 18 F-fluorodihydrotestosterone ( 18 F-FDHT) PET (10,11).…”

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confidence: 99%

“…Tumor ER expression can be visualized by 18 F-fluoroestradiol ( 18 F-FES) PET in breast cancer patients (9). AR expression in prostate cancer patients has been evaluated using 18 F-fluorodihydrotestosterone ( 18 F-FDHT) PET (10,11). If 18 F-FDHT PET is also able to determine the AR status in metastatic breast cancer patients, this technique has the potential to select patients eligible for AR-targeted therapies.…”

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confidence: 99%

“…If 18 F-FDHT PET is also able to determine the AR status in metastatic breast cancer patients, this technique has the potential to select patients eligible for AR-targeted therapies. The aim of the present study was to assess whether uptake on 18 F-FES and 18 F-FDHT PET correlates with levels of both ER and AR expression on a simultaneous biopsied metastasis.…”

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Androgen and Estrogen Receptor Imaging in Metastatic Breast Cancer Patients as a Surrogate for Tissue Biopsies

et al. 2017

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In addition to the well-known estrogen receptor (ER) and human epidermal growth factor receptor 2, the androgen receptor (AR) is also a potential drug target in breast cancer treatment. Whole-body imaging can provide information across lesions within a patient. ER expression in tumor lesions can be visualized by F-fluoroestradiol (F-FES) PET, and AR expression has been visualized in prostate cancer patients with F-fluorodihydrotestosterone (F-FDHT) PET. Our aim was to assess the concordance between F-FDHT andF-FES PET and tumor AR and ER expression measured immunohistochemically in patients with metastatic breast cancer. Patients with ER-positive metastatic breast cancer were eligible for the study, irrespective of tumor AR status. The concordance ofF-FDHT and F-FES uptake on PET with immunohistochemical expression of AR and ER in biopsies of corresponding metastases was analyzed. Patients underwentF-FDHT PET and F-FES PET. A metastasis was biopsied within 8 wk of the PET procedures. Tumor samples with more than 10% and 1% nuclear tumor cell staining were considered, respectively, AR- and ER-positive. Correlations between PET uptake and semiquantitative immunohistochemical scoring (percentage positive cells × intensity) were calculated. The optimum threshold of SUV to discriminate positive and negative lesions for both AR and ER was determined by receiver-operating-characteristic analysis. In the 13 evaluable patients, correlation ( ) between semiquantitative AR expression and F-FDHT uptake was 0.47 ( = 0.01) and between semiquantitative ER expression and F-FES uptake 0.78 ( = 0.01). The optimal cutoff for AR-positive lesions was an SUV of 1.94 for F-FDHT PET, yielding a sensitivity of 91% and a specificity of 100%; the optimal cutoff was an SUV of 1.54 for F-FES PET, resulting in a sensitivity and specificity of 100% for ER.F-FDHT and F-FES uptake correlate well with AR and ER expression levels in representative biopsies. These results show the potential use of whole-body imaging for receptor status assessment, particularly in view of biopsy-associated sampling errors and heterogeneous receptor expression in breast cancer metastases.

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Breast PET/MRI Hybrid Imaging and Targeted Tracers

Romeo

Helbich

Pinker

2022

Magnetic Resonance Imaging

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The recent introduction of hybrid positron emission tomography/magnetic resonance imaging (PET/MRI) as a promising imaging modality for breast cancer assessment has prompted fervent research activity on its clinical applications. The current knowledge regarding the possible clinical applications of hybrid PET/MRI is constantly evolving, thanks to the development and clinical availability of hybrid scanners, the development of new PET tracers and the rise of artificial intelligence (AI) techniques. In this state‐of‐the‐art review on the use of hybrid breast PET/MRI, the most promising advanced MRI techniques (diffusion‐weighted imaging, dynamic contrast‐enhanced MRI, magnetic resonance spectroscopy, and chemical exchange saturation transfer) are discussed. Current and experimental PET tracers (18F‐FDG, 18F‐NaF, choline, 18F‐FES, 18F‐FES, 89Zr‐trastuzumab, choline derivatives, 18F‐FLT, and 68Ga‐FAPI‐46) are described in order to provide an overview on their molecular mechanisms of action and corresponding clinical applications. New perspectives represented by the use of radiomics and AI techniques are discussed. Furthermore, the current strengths and limitations of hybrid PET/MRI in the real world are highlighted. Evidence Level 2 Technical Efficacy Stage 2

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Recommendations and Technical Aspects of 16α-[18F]Fluoro-17β-Estradiol PET to Image the Estrogen Receptor In Vivo

Cited by 43 publications

References 40 publications

¹⁸F-Fluoroestradiol PET Imaging of Activating Estrogen Receptor-α Mutations in Breast Cancer

¹⁸F-Fluoroestradiol PET Imaging of Activating Estrogen Receptor-α Mutations in Breast Cancer

Androgen and Estrogen Receptor Imaging in Metastatic Breast Cancer Patients as a Surrogate for Tissue Biopsies

Breast PET/MRI Hybrid Imaging and Targeted Tracers

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Recommendations and Technical Aspects of 16α-[18F]Fluoro-17β-Estradiol PET to Image the Estrogen Receptor In Vivo

Cited by 43 publications

References 40 publications

18F-Fluoroestradiol PET Imaging of Activating Estrogen Receptor-α Mutations in Breast Cancer

18F-Fluoroestradiol PET Imaging of Activating Estrogen Receptor-α Mutations in Breast Cancer

Androgen and Estrogen Receptor Imaging in Metastatic Breast Cancer Patients as a Surrogate for Tissue Biopsies

Breast PET/MRI Hybrid Imaging and Targeted Tracers

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Product

Resources

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¹⁸F-Fluoroestradiol PET Imaging of Activating Estrogen Receptor-α Mutations in Breast Cancer

¹⁸F-Fluoroestradiol PET Imaging of Activating Estrogen Receptor-α Mutations in Breast Cancer