Utility of 18F-fluoroestradiol (18F-FES) PET/CT imaging as a pharmacodynamic marker in patients with refractory estrogen receptor-positive solid tumors receiving Z-endoxifen therapy

Lin, Frank I.; Gonzalez, E. M.; Kummar, Shivaani; Do, Khanh; Shih, Joanna H.; Adler, S. S.; Kurdziel, Karen; Ton, Anita; Türkbey, Barış; Jacobs, Paula; Bhattacharyya, Sudeep; Chen, A. P.; Collins, Jerry M.; Doroshow, James H.; Choyke, Peter L.; Lindenberg, Maria Liza

doi:10.1007/s00259-016-3561-8

Cited by 29 publications

(97 citation statements)

References 34 publications

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“…With serial 18 F-FES PET scans in patients treated with ER modulators such as fulvestrant, we were able to visualize residual ER availability during therapy, which was associated with early progression (22). For other ER modulators such as GDC0810 and Z-endoxifen, 18 F-FES PET provided information about ER occupancy and guided dose selection for phase II trials (23,24). 18 F-FDHT uptake in tumor lesions of patients with prostate cancer diminished in 3 patients after treatment with a high dose of testosterone.…”

Section: Discussionmentioning

confidence: 99%

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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Section: Discussionmentioning

confidence: 99%

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

et al. 2017

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“…Patients received 40-300 mg/d orally for 28 d per cycle. In 8 of 15 patients who underwent imaging with 18 F-FES PET at baseline, uptake in tumor lesions (n 5 41) was seen (50). In these 8 patients, 18 F-FES PET was repeated early after administration of Z-endoxifen (1-5 d).…”

Section: Antihormonal Therapy and 18 F-fes Pet Or 18 F-fdht Petmentioning

confidence: 99%

Molecular Imaging in Cancer Drug Development

et al. 2018

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Development of new oncology drugs has increased since the improved understanding of cancer's complex biology. The oncology field has become the top therapeutic research area for new drugs. However, only a limited number of drugs entering clinical trials will be approved for use as the standard of care for cancer patients. Molecular imaging is increasingly perceived as a tool to support go/no-go decisions early during drug development. It encompasses a wide range of techniques that include radiolabeling a compound of interest followed by visualization with SPECT or PET. Radiolabeling can be performed using a variety of radionuclides, which are preferably matched to the compound on the basis of size and half-life. Imaging can provide information on drug behavior in vivo, whole-body drug target visualization, and heterogeneity in drug target expression. This review focuses on current applications of molecular imaging in the development of small molecules, antibodies, and antihormonal anticancer drugs.

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“…18 F]-FES is a PET tracer that is used in clinical practice to image the oestrogen receptor (ER) in breast cancer and the most widely studied ER (Lin et al, 2017;Venema et al, 2017), but its potential suitability for imaging of ER in the human brain has not yet been systematically investigated. The ER consists of two isoforms, ERa and ERb, which have distinct biologic functions.…”

Section: Discussionmentioning

confidence: 99%

Using positron emission tomography to investigate hormone-mediated neurochemical changes across the female lifespan: implications for depression

Zsido

Villringer

Sacher

2017

International Review of Psychiatry

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Ovarian hormones, particularly oestrogen and progesterone, undergo major fluctuations across the female lifespan. These hormone transition periods, such as the transition from pregnancy to postpartum, as well as the transition into menopause (perimenopause), are also known to be times of elevated susceptibility to depression. This study reviews how these transition periods likely influence neurochemical changes in the brain that result in disease vulnerability. While there are known associations between oestrogen/progesterone and different monoaminergic systems, the interactions and their potential implications for mood disorders are relatively unknown. Positron Emission Tomography (PET) allows for the in-vivo quantification of such neurochemical changes, and, thus, can provide valuable insight into how both subtle and dramatic shifts in hormones contribute to the elevated rates of depression during pre-menstrual, post-partum, and perimenopausal periods in a woman's life. As one better understands how to address the challenges of PET studies involving highly vulnerable populations, such as women who have recently given birth, one will gain the insight necessary to design and individualize treatment and therapy. Understanding the precise time-line in younger women when dramatic fluctuations in the hormonal milieu may contribute to brain changes may present a powerful opportunity to intervene before a vulnerable state develops into a diseased state in later life. ARTICLE HISTORY

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Utility of 18F-fluoroestradiol (18F-FES) PET/CT imaging as a pharmacodynamic marker in patients with refractory estrogen receptor-positive solid tumors receiving Z-endoxifen therapy

Abstract: F-FES PET imaging could serve as a pharmacodynamic biomarker for patients treated with ER-directed therapy.

Cited by 29 publications

References 34 publications

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

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

Molecular Imaging in Cancer Drug Development

Using positron emission tomography to investigate hormone-mediated neurochemical changes across the female lifespan: implications for depression

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