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Uterine Uptake of Estrogen and Progestogen-Based Radiotracers in Rhesus Macaques with Endometriosis

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Abstract

Purpose

Endometriosis is an estrogen-dependent disorder of menstruating primates where tissues similar to the inner lining of the uterus exist “ectopically” outside of the uterus. The ectopic endometrium, like the endometrium within the uterus, expresses estrogen receptors (ER) and progesterone receptors (PR) and undergoes hormone-dependent cell proliferation and bleeding each menstrual cycle. The goal of this study was to conduct abdominopelvic positron emission tomography (PET) scans with computed tomography (CT) imaging of rhesus macaques (Macaca mulatta) using radiotracers that target ER and PR [16α-[18F]fluoroestradiol (FES) and 12-[18F]fluoro-furanyl-nor-progesterone (FFNP)] in individuals with and without endometriosis. We also aimed to determine if menstrual cycle phase and/or the presence of endometriosis affected the uptake of these radiotracers.

Procedures

Rhesus macaques with either clinically diagnosed endometriosis (n = 6) or no endometriosis (n = 4) underwent PET/CT scans with FES. A subset of the animals also underwent PET/CT scans with FFNP. Standard uptake values corrected for body weight (SUVs) were obtained for each radiotracer in target and background tissues (e.g., intestinal). We performed repeated measure analysis of variance tests to determine how uterine and background uptake differed with scan time, phase of the menstrual cycle, and disease state.

Results

Abdominopelvic PET/CT could not resolve small, individual endometriotic lesions. However, macaques with endometriosis displayed higher uterine uptake compared to those without the disorder. Radiotracer uptake differed by menstrual cycle phase with increased uterine uptake of both radiotracers in the proliferative phase of the menstrual cycle. Background intestinal uptake of FFNP increased over time after infusion, but only during the proliferative phase.

Conclusions

PET/CT with FES and FFNP support the concept that ER and PR levels are altered in individuals with endometriosis. This highlights the impact of the disease on typical reproductive tract function and may provide a novel pathway for the identification of individuals with endometriosis.

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Data Availability

The data presented in this study are available on request from the corresponding author.

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Acknowledgements

We would like to Addie Luo for her assistance with procedures and manuscript preparation. We would also like to thank the veterinary staff at the Oregon National Primate Research Center for all their work in performing these PET scans. And finally, we would like to thank the chemists at Oregon Health and Science’s Center for Radiochemistry Research and the Primate Multimodality Imaging Center.

Funding

Grant support: NIH NICHD P01HD106485, P51OD011092, and F32HD107809.

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Authors and Affiliations

  1. Department of Biology, Whitman College, Walla Walla, WA, USA

    Rachel C. Wilson

  2. Center for Radiochemistry Research, Oregon Health & Science University, Portland, OR, USA

    Jeanne M. Link

  3. Department of Radiology, University of North Carolina, Chapel Hill, NC, USA

    Yueh Z. Lee & Jorge D. Oldan

  4. Division of Reproduction Endocrinology and Infertility, Department of Obstetrics and Gynecology, Duke University School of Medicine, Durham, NC, USA

    Steven L. Young

  5. Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR, USA

    Ov D. Slayden

  6. Department of Obstetrics and Gynecology, Oregon Health & Science University, Portland, OR, USA

    Ov D. Slayden

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  1. Rachel C. Wilson
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Correspondence to Rachel C. Wilson.

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Wilson, R.C., Link, J.M., Lee, Y.Z. et al. Uterine Uptake of Estrogen and Progestogen-Based Radiotracers in Rhesus Macaques with Endometriosis. Mol Imaging Biol 26, 334–343 (2024). https://doi.org/10.1007/s11307-023-01892-9

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  • DOI: https://doi.org/10.1007/s11307-023-01892-9

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