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Cross-Species Physiological Assessment of Brain Estrogen Receptor Expression Using 18F-FES and 18F-4FMFES PET Imaging

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Abstract

Purpose

A retrospective analysis was performed of preclinical and clinical data acquired during the evaluation of the estrogen receptor (ER) PET tracer 4-fluoro-11β-methoxy-16α-[18F]-fluoroestradiol (4FMFES) and its comparison with 16α-[18F]-fluoroestradiol (FES) in mice, rats, and humans with a focus on the brain uptake.

Procedures

Breast cancer tumor-bearing female BALB/c mice from a previous study and female Sprague-Dawley rats (control and ovariectomized) were imaged by 4FMFES or FES-PET imaging. Immediately after, low-dose CT was performed in the same bed position. Semi-quantitative analysis was conducted to extract %ID/g data. Small cohorts of mice and rats were imaged with 4FMFES in an ultra-high-resolution small animal PET scanner prototype (LabPET II). Rat brains were dissected and imaged separately with both PET and autoradiography. In parallel, 31 breast cancer patients were enrolled in a clinical phase II study to compare 4FMFES with FES for oncological assessment. Since the head was included in the field of view, brain uptake of discernable foci was measured and reported as SUVMax.

Results

Regardless of the species studied, 4FMFES and FES uptake were relatively uniform in most regions of the brain, except for bilateral foci at the base of the skull, at the midsection of the brain. Anatomical localization of the PET signal using CT image fusion indicates that the signal origins from the pituitary in all studied species. 4FMFES yielded lower pituitary uptake than FES in patients, but an inverse trend was observed in rodents. 4FMFES pituitary contrast was higher than FES in all assessed groups. High-resolution small animal imaging of the brain of rats and mice revealed a supplemental signal anterior to the pituitary, which is likely to be the medial preoptic area. Dissection data further confirmed those findings and revealed additional signals corresponding to the arcuate and ventromedial nuclei, along with the medial and cortical amygdala.

Conclusion

4FMFES allowed visualization of ER expression in the pituitary in humans and two different rodent species with better contrast than FES. Improvement in clinical spatial resolution might allow visualization and analysis of other ER-rich brain areas in humans. Further work is now possible to link 4FMFES pituitary uptake to cognitive functions.

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Funding

This project was indirectly funded by the Canadian Breast Cancer Foundation (CBCF) for the clinical portion, as well as the Natural Sciences and Engineering Research Council of Canada for the development of the scanners. The preclinical studies were carried out with the support of the Sherbrooke Molecular Imaging Center and the Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke (CRCHUS).

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Authors and Affiliations

  1. Department of Nuclear Medicine and Radiobiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada

    Michel Paquette, Serge Phoenix, Jacques A. Rousseau, Brigitte Guérin, Éric E. Turcotte & Roger Lecomte

  2. Sherbrooke Molecular Imaging Center, Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke (CRCHUS), Sherbrooke, QC, Canada

    Michel Paquette, Serge Phoenix, Éric Lavallée, Jacques A. Rousseau, Brigitte Guérin, Éric E. Turcotte & Roger Lecomte

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  1. Michel Paquette
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  2. Serge Phoenix
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  3. Éric Lavallée
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  4. Jacques A. Rousseau
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Corresponding author

Correspondence to Michel Paquette.

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Conflict of Interest

RL is a co-founder and chief scientific officer of IR&T Inc. who was involved in the development of the prototype ultra-high-resolution PET scanner LabPET II. The other authors have no conflict of interest to declare regarding this paper or the results therein.

Ethical Approval

All animal procedures were approved by the Ethical Committee for Animal Care of the Université de Sherbrooke, in compliance with the policies and directives of the Canadian Council on Animal Care. Patients were retroactively analyzed from a previously reported phase II breast cancer clinical trial evaluating 4FMFES-PET, which was performed under the authority of Health Canada and approved by the Sherbrooke University Hospital Clinical Research Ethics Committee and Institutional Board.

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Paquette, M., Phoenix, S., Lavallée, É. et al. Cross-Species Physiological Assessment of Brain Estrogen Receptor Expression Using 18F-FES and 18F-4FMFES PET Imaging. Mol Imaging Biol 22, 1403–1413 (2020). https://doi.org/10.1007/s11307-020-01520-w

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  • DOI: https://doi.org/10.1007/s11307-020-01520-w

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