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Imaging of Estrogen Receptor-α in Rat Pial Arterioles using a Digital Immunofluorescent Microscope
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Pharmacodynamic imaging guides dosing of a selective estrogen receptor degrader

Pedram Heidari1, Francis Deng2, Shadi A Esfahani1

  • 1Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|January 23, 2015
PubMed
Abstract

Insights

16α-(18)F-fluoroestradiol (FES) PET imaging can optimize estrogen receptor (ER) targeted therapy dosing for breast cancer. This study shows FES uptake reflects ER blockade, guiding treatment decisions.

Area of Science:

  • Oncology
  • Nuclear Medicine
  • Pharmacology

Background:

  • Estrogen receptor (ER) targeting is crucial for managing ER-positive breast cancer.
  • Current anti-ER therapy lacks methods for dose optimization.
  • Estrogen receptor-positive breast cancer treatment requires precise dosing strategies.

Purpose of the Study:

  • To assess the utility of 16α-(18)F-fluoroestradiol (FES) PET for optimizing fulvestrant dosing.
  • To evaluate FES PET as a tool for monitoring anti-ER therapy efficacy.
  • To establish a preclinical model for fulvestrant dose optimization using PET imaging.

Main Methods:

  • In vitro analysis of FES retention, ERα protein, and ESR1 mRNA in MCF7 cells treated with varying fulvestrant doses.
  • MCF7 xenografts in mice were treated with vehicle or different fulvestrant doses (0.05 mg, 0.5 mg, 5 mg).
  • PET/CT scans using (18)F-FES and (18)F-FDG were performed; ER expression and proliferation (Ki67) were assessed post-treatment.

Main Results:

  • In vitro, (18)F-FES uptake and ER expression decreased in a dose-dependent manner with fulvestrant, despite increased ER mRNA.
  • In xenografts, fulvestrant significantly reduced ER expression dose-dependently, with stable mRNA and proliferation markers across groups.
  • A significant dose-dependent reduction in (18)F-FES PET SUV(mean) was observed with fulvestrant, unlike (18)F-FDG PET.

Conclusions:

  • (18)F-FES uptake accurately reflects dose-dependent ER degradation/blockade by fulvestrant.
  • Changes in (18)F-FES uptake precede alterations in tumor metabolism and proliferation.
  • (18)F-FES PET can guide ER-targeted therapy dosing and monitor early treatment efficacy in breast cancer patients.

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