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. Author manuscript; available in PMC: 2023 Jan 23.
Published in final edited form as: Clin Nucl Med. 2022 Sep 6;48(1):e26–e27. doi: 10.1097/RLU.0000000000004385

A tale of 3 tracers: Contrasting uptake patterns of 18F-fluciclovine, 68Ga-PSMA, and 18F-FDG in the uterus and adnexa

Ismaheel O Lawal 1,2, Omotayo Atinuke Adediran 1, Saima Muzahir 1, Sarah Friend 3, Manali Ajay Bhave 4, Jane Meisel 3, Mylin A Torres 5, Toncred Marya Styblo 6, Cathy Graham 6, Anna Holbrook 1, Kevin Kalinsky 3, Bridget Fielder 1, Ronald J Crowe 7, Gary A Ulaner 8, David M Schuster 1
PMCID: PMC9869918  NIHMSID: NIHMS1860710  PMID: 36469077

Abstract

A 41-year-old woman with newly diagnosed invasive lobular carcinoma of the breast underwent sequential 68Ga-PSMA-11 PET/CT and 18F-fluciclovine PET/CT as part of an ongoing clinical trial (NCT04750473). 68Ga-PSMA PET/CT showed increased radiotracer uptake in the uterine endometrium and left adnexa. 18F-fluciclovine PET/CT showed increased radiotracer uptake in an enlarged uterus in a known uterine leiomyoma. A clinical 18F-FDG PET/CT demonstrated radiotracer uptake in the endometrium and a circumferential area of uptake in the left adnexa, a pattern more similar to the 68Ga-PSMA uptake pattern. This case highlights the discordance in the uptake pattern of two radiotracers in different benign gynecological conditions. While these tracers are approved for prostate cancer imaging, they are increasingly being used in other malignancies.

Keywords: 68Ga-PSMA PET, 18F-fluciclovin PET, uterine leiomyoma, luteal cyst, endometrium, adnexa mass

Figure 1.

Figure 1.

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A 41-year-old woman with newly diagnosed invasive lobular carcinoma of the right breast was enrolled into a clinical trial comparing the performance of 68Ga-PSMA-11 and 18F-fluciclovine PET/CT in lobular breast cancer. 68Ga-PSMA PET/CT images of the patient (A) showed increased radiotracer uptake in the endometrium (straight arrows) and in the left adnexa (curved arrow). There is no significant 68Ga-PSMA uptake in the uterine myometrium. A review of the menstrual history of the patient revealed that she was in the secretory phase of her cycle during the PET/CT scans, suggesting that the endometrial and left adnexal uptake are related to ovulation. By contrast, 18F-fluciclovine PET/CT images (B) acquired 24 hours after the 68Ga-PSMA PET/CT study showed increased radiotracer uptake in the myometrium (arrows). The patient has a history of uterine leiomyoma. 68Ga-PSMA and 18F-fluciclovine are approved for prostate cancer imaging.1,2 Yet, both radiotracers are not prostate cancer-specific and are increasingly being evaluated in other malignancies.3–5 PSMA is expressed in the neovasculature of tumors, including endometrial carcinoma.6 However, the homogeneous 68Ga-PSMA uptake in the endometrium and adnexa of this patient without clinical suspicion of endometrial carcinoma is similar to the known pattern of 18F-FDG uptake in the uterus and adnexa during the different phases of the menstrual cycle - a mid-cycle ovulatory phase rise in endometrial uptake with a subsequent decline and a luteal phase increased ovarian uptake.7,8 In (C), 18F-FDG PET/CT images of this patient obtained four days after the 18F-fluciclovine PET/CT scan showed increased radiotracer uptake in the endometrium (straight arrows) and circumferential area of uptake in the left adnexa (curved arrows), demonstrating a pattern of uptake similar to the pattern seen on the 68Ga-PSMA PET/CT images. No significant uptake of 18F-fluciclovine is seen in the endometrium or the adnexa while 18F-FDG and 68Ga-PSMA PET/CT showed no significant radiotracer uptake in the leiomyomatous myometrium. This contrasting patterns of uptake between these three radiotracers is probably driven by the difference in the target engagement of the two radiotracers. 18F-fluciclovine is a radio-halogenated synthetic amino acid with known time-dependent physiologic uptake in muscles.9 Since leiomyoma is a benign tumor of the uterine smooth muscle cells, 18F-fluciclovine uptake in it is congruent with the bio-distribution of the radiotracer. Increased 18F-PSMA-1007 has been previously reported in corpus luteal cyst.10 This case, for the first time, presents a contrasting pattern of uptake of 68Ga-PSMA and 18F-fluciclovine and their relationship with the well-known uptake pattern of 18F-FDG in different benign gynecological conditions. The two radiotracers (68Ga-PSMA and 18F-fluciclovine), which are commonly used in prostate cancer imaging, have the potential for use in imaging gynecological malignancies. Also, 18F-FES, a PET radiotracer that targets the estrogen receptor, was recently approved for breast cancer imaging. Uptake of 18F-FES in the endometrium (more in the proliferative phase than luteal phase) and the myometrium has also being reported.11,12 Because cancerous and non-cancerous entities can co-occur, a working knowledge of the behavior of these tracers in non-malignant conditions is necessary to inform the accurate interpretation of PET/CT scans with these tracers acquired for oncological indications.

Figure 2.

Figure 2.

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A contrast-enhanced CT (C) acquired 5 days prior to the 68Ga-PSMA PET/CT scan demonstrating leiomyoma of the uterus and left adnexa, identified as a luteal cyst. This left luteal cyst corresponds to the area of diffuse 68Ga-PSMA uptake and circumferential 18F-FDG uptake on the respective PET/CT scans.

Acknowledgements:

Study funded by NIH R21CA256280.

Footnotes

Conflict of interest: Fluciclovine doses provided by Blue Earth Diagnostics, Inc. PSMA-11 cold kits provided by Telix Pharmaceuticals (US) Inc.

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