Literature DB >> 25609068

Pharmacodynamic imaging guides dosing of a selective estrogen receptor degrader.

Pedram Heidari1, Francis Deng2, Shadi A Esfahani1, Alicia K Leece1, Timothy M Shoup3, Neil Vasdev3, Umar Mahmood4.   

Abstract

PURPOSE: Estrogen receptor (ER) targeting is key in management of receptor-positive breast cancer. Currently, there are no methods to optimize anti-ER therapy dosing. This study assesses the use of 16α-(18)F-fluoroestradiol ((18)F-FES) PET for fulvestrant dose optimization in a preclinical ER(+) breast cancer model. EXPERIMENTAL
DESIGN: In vitro, (18)F-FES retention was compared with ERα protein expression (ELISA) and ESR1 mRNA transcription (qPCR) in MCF7 cells (ER(+)) after treatment with different fulvestrant doses. MCF7 xenografts were grown in ovariectomized nude mice and assigned to vehicle, low- (0.05 mg), medium- (0.5 mg), or high-dose (5 mg) fulvestrant treatment groups (5-7 per group). Two and 3 days after fulvestrant treatment, PET/CT was performed using (18)F-FES and (18)F-FDG, respectively. ER expression was assessed by immunohistochemistry, ELISA, and qPCR on xenografts. Tumor proliferation was assessed using Ki67 immunohistochemistry.
RESULTS: In vitro, we observed a parallel graded reduction in (18)F-FES uptake and ER expression with increased fulvestrant doses, despite enhancement of ER mRNA transcription. In xenografts, ER expression significantly decreased with increased fulvestrant dose, despite similar mRNA expression and Ki67 staining among the treatment groups. We observed a significant dose-dependent reduction of (18)F-FES PET mean standardized uptake value (SUV(mean)) with fulvestrant treatment but no significant difference among the treatment groups in (18)F-FDG PET SUV(mean).
CONCLUSIONS: We demonstrated that (18)F-FES uptake mirrors the dose-dependent changes in functional ER expression with fulvestrant resulting in ER degradation and/or blockade; these precede changes in tumor metabolism and proliferation. Quantitative (18)F-FES PET may be useful for tracking early efficacy of ER blockade/degradation and guiding ER-targeted therapy dosing in patients with breast cancer. ©2015 American Association for Cancer Research.

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Year:  2015        PMID： 25609068      PMCID： PMC4359957          DOI： 10.1158/1078-0432.CCR-14-1178

Source DB:  PubMed          Journal:  Clin Cancer Res        ISSN： 1078-0432            Impact factor:   12.531


  39 in total

1.  Comparison of the short-term biological effects of 7alpha-[9-(4,4,5,5,5-pentafluoropentylsulfinyl)-nonyl]estra-1,3,5, (10)-triene-3,17beta-diol (Faslodex) versus tamoxifen in postmenopausal women with primary breast cancer.

Authors:  J F Robertson; R I Nicholson; N J Bundred; E Anderson; Z Rayter; M Dowsett; J N Fox; J M Gee; A Webster; A E Wakeling; C Morris; M Dixon
Journal:  Cancer Res       Date:  2001-09-15       Impact factor: 12.701

2.  Fulvestrant (ICI 182,780)-dependent interacting proteins mediate immobilization and degradation of estrogen receptor-alpha.

Authors:  Xinghua Long; Kenneth P Nephew
Journal:  J Biol Chem       Date:  2006-02-03       Impact factor: 5.157

3.  Three dose regimens of fulvestrant in postmenopausal Japanese women with advanced breast cancer: results from a double-blind, phase II comparative study (FINDER1).

Authors:  S Ohno; Y Rai; H Iwata; N Yamamoto; M Yoshida; H Iwase; N Masuda; S Nakamura; H Taniguchi; S Kamigaki; S Noguchi
Journal:  Ann Oncol       Date:  2010-05-21       Impact factor: 32.976

4.  Double-blind, randomized trial comparing the efficacy and tolerability of fulvestrant versus anastrozole in postmenopausal women with advanced breast cancer progressing on prior endocrine therapy: results of a North American trial.

Authors:  C K Osborne; J Pippen; S E Jones; L M Parker; M Ellis; S Come; S Z Gertler; J T May; G Burton; I Dimery; A Webster; C Morris; R Elledge; A Buzdar
Journal:  J Clin Oncol       Date:  2002-08-15       Impact factor: 44.544

5.  Quantitative imaging of estrogen receptor expression in breast cancer with PET and 18F-fluoroestradiol.

Authors:  Lanell M Peterson; David A Mankoff; Thomas Lawton; Kevin Yagle; Erin K Schubert; Svetlana Stekhova; Allen Gown; Jeanne M Link; Timothy Tewson; Kenneth A Krohn
Journal:  J Nucl Med       Date:  2008-02-20       Impact factor: 10.057

6.  Predicting Breast Cancer Endocrine Responsiveness Using Molecular Imaging.

Authors:  Erin Currin; Hannah M Linden; David A Mankoff
Journal:  Curr Breast Cancer Rep       Date:  2011-12

7.  The detection of ESR1/PGR/ERBB2 mRNA levels by RT-QPCR: a better approach for subtyping breast cancer and predicting prognosis.

Authors:  Xin Du; Xiao-Qing Li; Lin Li; Yuan-Yuan Xu; Yu-Mei Feng
Journal:  Breast Cancer Res Treat       Date:  2013-02-10       Impact factor: 4.872

8.  Positron tomographic assessment of estrogen receptors in breast cancer: comparison with FDG-PET and in vitro receptor assays.

Authors:  F Dehdashti; J E Mortimer; B A Siegel; L K Griffeth; T J Bonasera; M J Fusselman; D D Detert; P D Cutler; J A Katzenellenbogen; M J Welch
Journal:  J Nucl Med       Date:  1995-10       Impact factor: 10.057

9.  Hormone sensitivity in breast cancer: influence of heterogeneity of oestrogen receptor expression and cell proliferation.

Authors:  R I Nicholson; N Bouzubar; K J Walker; R McClelland; A R Dixon; J F Robertson; I O Ellis; R W Blamey
Journal:  Eur J Cancer       Date:  1991       Impact factor: 9.162

10.  Hormone receptor status, tumor characteristics, and prognosis: a prospective cohort of breast cancer patients.

Authors:  Lisa K Dunnwald; Mary Anne Rossing; Christopher I Li
Journal:  Breast Cancer Res       Date:  2007       Impact factor: 6.466
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  20 in total

1.  Heterogeneity in Metastatic Breast Cancer 18F-Fluoroestradiol Uptake: Clinically Actionable, Biologically Illuminating?

Authors:  Brenda F Kurland; Steffi Oesterreich
Journal:  J Nucl Med       Date:  2018-06-14       Impact factor: 10.057

2.  Imaging of Secreted Extracellular Periostin, an Important Marker of Invasion in the Tumor Microenvironment in Esophageal Cancer.

Authors:  Pedram Heidari; Shadi A Esfahani; Nazife S Turker; Gabrielle Wong; Timothy C Wang; Anil K Rustgi; Umar Mahmood
Journal:  J Nucl Med       Date:  2015-06-11       Impact factor: 10.057

3.  Design, construction and testing of a low-cost automated (68)Gallium-labeling synthesis unit for clinical use.

Authors:  Pedram Heidari; Alicia Szretter; Laura E Rushford; Maria Stevens; Lee Collier; Judit Sore; Jacob Hooker; Umar Mahmood
Journal:  Am J Nucl Med Mol Imaging       Date:  2016-07-06

4.  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.

Authors:  Frank I Lin; E M Gonzalez; S Kummar; K Do; J Shih; S Adler; K A Kurdziel; A Ton; B Turkbey; P M Jacobs; S Bhattacharyya; A P Chen; J M Collins; J H Doroshow; P L Choyke; M L Lindenberg
Journal:  Eur J Nucl Med Mol Imaging       Date:  2016-11-21       Impact factor: 9.236

5.  18F-16α-17β-Fluoroestradiol Binding Specificity in Estrogen Receptor-Positive Breast Cancer.

Authors:  Kelley Salem; Manoj Kumar; Ginny L Powers; Justin J Jeffery; Yongjun Yan; Aparna M Mahajan; Amy M Fowler
Journal:  Radiology       Date:  2017-09-25       Impact factor: 11.105

Review 6.  Receptor Occupancy Imaging Studies in Oncology Drug Development.

Authors:  Ingrid J G Burvenich; Sagun Parakh; Adam C Parslow; Sze Ting Lee; Hui K Gan; Andrew M Scott
Journal:  AAPS J       Date:  2018-03-08       Impact factor: 4.009

7.  18F-Fluoroestradiol PET/CT Measurement of Estrogen Receptor Suppression during a Phase I Trial of the Novel Estrogen Receptor-Targeted Therapeutic GDC-0810: Using an Imaging Biomarker to Guide Drug Dosage in Subsequent Trials.

Authors:  Yingbing Wang; Karen L Ayres; Debra A Goldman; Maura N Dickler; Aditya Bardia; Ingrid A Mayer; Eric Winer; Jill Fredrickson; Carlos L Arteaga; José Baselga; Henry C Manning; Umar Mahmood; Gary A Ulaner
Journal:  Clin Cancer Res       Date:  2016-12-23       Impact factor: 12.531

8.  Determination of binding affinity of molecular imaging agents for steroid hormone receptors in breast cancer.

Authors:  Kelley Salem; Manoj Kumar; Kyle C Kloepping; Ciara J Michel; Yongjun Yan; Amy M Fowler
Journal:  Am J Nucl Med Mol Imaging       Date:  2018-04-25

9.  Estrogen Receptor Binding (18F-FES PET) and Glycolytic Activity (18F-FDG PET) Predict Progression-Free Survival on Endocrine Therapy in Patients with ER+ Breast Cancer.

Authors:  Brenda F Kurland; Lanell M Peterson; Jean H Lee; Erin K Schubert; Erin R Currin; Jeanne M Link; Kenneth A Krohn; David A Mankoff; Hannah M Linden
Journal:  Clin Cancer Res       Date:  2016-06-24       Impact factor: 12.531

Review 10.  The quest for improving the management of breast cancer by functional imaging: The discovery and development of 16α-[18F]fluoroestradiol (FES), a PET radiotracer for the estrogen receptor, a historical review.

Authors:  John A Katzenellenbogen
Journal:  Nucl Med Biol       Date:  2020-02-22       Impact factor: 2.408
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