FES-PET/CT Imaging for Breast Cancer

Overseen By Regan Butterfield Schuchart

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Utah

Must be taking: Antihormonal therapy

Must not be taking: Estrogen receptor agonists

Disqualifiers: Pregnancy, Breastfeeding, Medically unstable, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a special imaging technique, FES PET/CT, to better understand breast cancer, specifically invasive lobular cancer. The goal is to assess how effectively this imaging method aids in diagnosing and tracking this cancer type. Participants will undergo a special scan after receiving a small amount of a tracer ([18F]Fluoroestradiol, also known as Cerianna), which highlights cancer cells during imaging. Those with confirmed invasive lobular breast cancer, whether newly diagnosed or with a history of the disease, might be suitable candidates. As a Phase 2 trial, this research focuses on evaluating the imaging technique's effectiveness in an initial, smaller group, offering participants a chance to contribute to advancements in cancer diagnosis.

Do I have to stop taking my current medications for the trial?

If you are taking estrogen receptor agonists like fulvestrant or tamoxifen, you must stop them at least 5 weeks before the FES-PET/CT scan. However, if you are on aromatase inhibitors or luteinizing hormone-releasing hormone agonists, you do not need to stop them. If you are in Exploratory Arm 1, you can continue your current antihormonal therapy or chemotherapy.

What prior data suggests that FES PET/CT imaging is safe for breast cancer patients?

Research has shown that [18F]Fluoroestradiol (FES) PET/CT is generally safe for people. This imaging method has received approval in the United States for certain breast cancer cases, indicating that the FDA has deemed it safe for similar uses.

In studies, most patients who underwent FES PET/CT did not experience serious side effects. The procedure uses a small amount of a special compound that binds to estrogen receptors, enhancing the visibility of tumors in scans.

Safety monitoring committees frequently oversee these studies to ensure participant safety. While no treatment is entirely without risk, the existing approval and oversight indicate that FES PET/CT is considered safe for most patients. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the FES-PET/CT imaging technique for breast cancer because it offers a unique way to visualize estrogen receptor activity in tumors. Unlike standard imaging methods, this technique uses [18F]Fluoroestradiol (FES), a radioactive tracer that binds specifically to estrogen receptors, providing a more precise picture of how the cancer might respond to hormone therapy. By offering a clearer view of receptor status, FES-PET/CT could help tailor treatments more effectively for patients with estrogen receptor-positive invasive lobular carcinoma, potentially improving outcomes and avoiding unnecessary treatments.

What evidence suggests that FES PET/CT imaging is effective for invasive lobular cancer?

Research shows that [18F]Fluoroestradiol (FES) PET/CT is a promising method for imaging invasive lobular cancer (ILC). Studies have found that FES PET/CT can accurately detect cancer sites with estrogen receptors, with one study finding true-positive results in 97% of cases. This trial will evaluate FES PET/CT in two phases: the Pilot Phase and the Expansion Phase. Participants in both phases will undergo an FES PET/CT scan, which attaches to estrogen receptors, helping doctors locate the cancer and providing a clearer picture for treatment planning. This method is especially helpful because traditional imaging methods like FDG-PET/CT often miss ILC. Overall, FES PET/CT could improve how doctors diagnose and manage breast cancer, especially in cases that other scans might miss. ^{1 3 6 7 8}

Who Is on the Research Team?

Jeffrey Yap, PhD

Principal Investigator

Huntsman Cancer Institute/ University of Utah

Are You a Good Fit for This Trial?

This trial is for adults with invasive lobular carcinoma of the breast, confirmed within the past 12-16 weeks. Participants must be willing to provide blood samples and have their medical records reviewed. It's not for those who've had certain estrogen treatments recently, are pregnant or breastfeeding, or have severe allergies/autoimmune diseases.

Inclusion Criteria

Patient is willing to have their clinical records reviewed, and be contacted by phone during follow-up intervals specified, for approximately 60 months after enrollment

My cancer is ER- and has spread from the lobular area.

My cancer is ER+ and was confirmed by a biopsy within the last 16 weeks.

Exclusion Criteria

I had surgery to remove invasive lobular carcinoma.

I am not currently hospitalized or in need of urgent care.

You need special anesthesia monitoring for a PET/CT scan.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging Session

Participants undergo one session of [18F]FES PET/CT Imaging, with optional [18F]FDG PET/CT scan and optional follow-up [18F]FES PET/CT exam

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging

Up to 60 months

What Are the Treatments Tested in This Trial?

Interventions

• [18F]Fluoroestradiol (FES) PET/CT

Trial Overview [18F]Fluoroestradiol (FES) PET/CT imaging is being tested on patients with invasive lobular carcinoma to see how well it detects cancer spread and monitors treatment response over time.

How Is the Trial Designed?

Group I: Pilot Phase Experimental Treatment 1 Intervention

Subjects with biopsy-proven invasive lobular carcinoma (ILC), diagnosed within 12 weeks of imaging, confirmed from biopsy of primary tumor or metastasis, will undergo one Fluorine-18 (18F) -Fluoroestradiol (FES) positron emission tomography/computed tomography (PET/CT) scan and one optional 18F-fluorodeoxyglucose (FDG) PET/CT(if a standard of care scan not already performed). For the FES scan, patients are administered a dose of approximately 6 millicurie (mCi) and imaged approximately 60 minutes after injection. For the FDG scan, patients are administered a dose of approximately 15 mCi and imaged approximately 60 minutes after injection.

Group II: Expansion Phase Experimental Treatment 1 Intervention

Subjects with histologically confirmed estrogen receptor positive (ER+) invasive lobular carcinoma (ILC), diagnosed within 16 weeks of imaging, confirmed from biopsy of primary tumor or metastasis, will undergo one 18F-Fluoroestradiol (FES) PET/CT scan, one optional 18F-FDG PET/CT (if a standard of care scan not already performed), and one optional follow-up FES-PET/CT. For the FES scan, patients are administered a dose of approximately 6 mCi and imaged approximately 60 minutes after injection. For the FDG scan, patients are administered a dose of approximately 15 mCi and imaged approximately 60 minutes after injection.

Who Is Running the Clinical Trial?

University of Utah

Lead Sponsor

Trials

1,169

Recruited

1,623,000+

Published Research Related to This Trial

The PET tracer 16α-18F-fluoro-17β-fluoroestradiol (18F-FES) is FDA-approved and offers a noninvasive method for assessing estrogen receptor status in breast cancer patients, which can help tailor therapy and improve outcomes.

18F-FES, marketed as Cerianna, is now under GE Healthcare's management and is designed to assist oncologists and surgeons in evaluating recurrent tumors and metastatic lesions effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

18F-FES Whole-Body Imaging Protocol for Evaluating Tumor Estrogen Receptor Status in Patients with Recurrent or Metastatic Breast Cancer. Grabher, BJ.[2023]

18F-FES PET imaging is an FDA-approved diagnostic tool for detecting estrogen receptor-positive lesions in patients with recurrent or metastatic breast cancer, allowing for noninvasive evaluation of ER functionality.

The Society of Nuclear Medicine and Molecular Imaging established appropriate use criteria for 18F-FES PET, highlighting its best applications in assessing ER status in challenging cases and guiding endocrine therapy decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Summary: Appropriate Use Criteria for Estrogen Receptor-Targeted PET Imaging with 16α-18F-Fluoro-17β-Fluoroestradiol. Ulaner, GA., Mankoff, DA., Clark, AS., et al.[2023]

An improved automated synthesis of the PET tracer 18F-Fluoroestradiol ([18F]FES) has been developed, yielding high radiochemical purity (>99%) and demonstrating stability for up to 24 hours, making it a reliable option for clinical use.

Clinical PET imaging studies show that [18F]FES specifically targets estrogen receptor-positive (ER+) breast cancer tissues, providing clearer delineation of these regions compared to [18F]FDG, which indicates its potential for better predicting hormone therapy responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical production, stability studies and PET imaging with 16-alpha-[18F]fluoroestradiol ([18F]FES) in ER positive breast cancer patients. Kumar, P., Mercer, J., Doerkson, C., et al.[2016]

In a study involving 33 breast cancer patients, (18)F-FES PET was found to significantly improve diagnostic understanding in 88% of cases and led to changes in therapy for 48% of patients, highlighting its potential as a valuable tool in clinical decision-making.

The (18)F-FES PET tracer was particularly effective in detecting bone metastases, identifying 341 lesions compared to 246 found through conventional imaging, although its sensitivity for liver metastases was limited due to high background activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PET imaging of estrogen receptors as a diagnostic tool for breast cancer patients presenting with a clinical dilemma. van Kruchten, M., Glaudemans, AW., de Vries, EF., et al.[2016]

18F-fluoroestradiol (18F-FES) is an FDA-approved radiopharmaceutical that enhances the molecular imaging of estrogen receptors in ER-positive breast cancer, particularly in metastatic cases.

The use of 18F-FES combined with PET imaging can aid in treatment selection and staging, as well as provide valuable insights into tumor heterogeneity and the specific imaging of lobular breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular Imaging for Estrogen Receptor-Positive Breast Cancer: Clinical Applications of Whole Body and Dedicated Breast Positron Emission Tomography. Goodman, K., Abel, MK., Lawhn-Heath, C., et al.[2023]

In a study of 312 FES PET scans from 239 patients with ER+ primary breast cancer, sex hormone-binding globulin (SHBG) was found to inversely affect FES uptake, indicating its importance in assessing estrogen receptor expression.

The study suggests that FES uptake can be reliably measured by adjusting for lean body mass (LBM), and that pre-menopausal estradiol levels do not significantly impact FES uptake, allowing for simplified imaging protocols without compromising accuracy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Factors influencing the uptake of 18F-fluoroestradiol in patients with estrogen receptor positive breast cancer. Peterson, LM., Kurland, BF., Link, JM., et al.[2021]

The estrogen analog 16 alpha-[18F]fluoroestradiol (FES) is an effective imaging agent for detecting estrogen receptor-positive breast tumors, and clinical studies are comparing its effectiveness with the metabolic probe 2-[18F]fluoro-2-deoxyglucose (FDG) in patients undergoing tamoxifen therapy.

Fluorine-18 labeled progestins have shown promising selective distribution in target tissues in animal studies and are ready for human imaging studies, although developing technetium-99m labeled steroids presents unique challenges.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The development of estrogen and progestin radiopharmaceuticals for imaging breast cancer. Katzenellenbogen, JA., Welch, MJ., Dehdashti, F.[2016]

The imaging agent 16α-18F-fluoro-17β-fluoroestradiol (18F-FES) is FDA-approved for use in patients with ER-positive breast cancer, aiding in the selection of appropriate endocrine therapies and assessing ER status in hard-to-biopsy lesions.

There are ongoing clinical trials for new progesterone receptor-targeted imaging agents, indicating a potential expansion of targeted imaging options for breast cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Estrogen Receptor-Targeted and Progesterone Receptor-Targeted PET for Patients with Breast Cancer. Ulaner, GA., Fowler, AM., Clark, AS., et al.[2023]

In a study of 16 patients with metastatic ER-positive breast cancer, the absence of estrogen receptor expression as measured by [18F]FES PET was a strong predictor of poor response to the treatment with rintodestrant, indicating that monitoring ER expression can guide treatment decisions.

The study found that [18F]FES uptake could effectively monitor the reversible effects of rintodestrant therapy, with no uptake in lesions during treatment suggesting a lack of response, while restoration of uptake after treatment indicated potential for continued therapeutic action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[18F]FDG and [18F]FES PET/CT Imaging as a Biomarker for Therapy Effect in Patients with Metastatic ER+ Breast Cancer Undergoing Treatment with Rintodestrant. Iqbal, R., Yaqub, M., Bektas, HO., et al.[2023]

The PET imaging agent [18F]16alpha-fluoroestradiol (FES) is effective for studying estrogen receptors in breast cancer, with a calculated effective dose equivalent of 0.022 mSv/MBq, indicating a low radiation exposure for patients.

The highest radiation dose was received by the liver, but overall, the radiation risks associated with FES imaging are comparable to other common nuclear medicine tests and are considered safe within accepted limits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[18F]fluoroestradiol radiation dosimetry in human PET studies. Mankoff, DA., Peterson, LM., Tewson, TJ., et al.[2016]

18F-FES PET imaging is an FDA-approved method for detecting estrogen receptor alpha (ER+) lesions in patients with recurrent or metastatic breast cancer, providing a non-invasive alternative to biopsy.

This imaging technique allows for the assessment of ER expression and function across multiple metastatic sites, helping to predict responses to endocrine therapy and understand tumor heterogeneity, which is crucial for personalized cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PET Imaging of Estrogen Receptors Using 18F-Based Radioligands. Kumar, M., Salem, K., Jeffery, JJ., et al.[2022]

Citations

1. pubs.rsna.org pubs.rsna.org/doi/full/10.1148/rg.220143

18F-Fluoroestradiol: Current Applications and Future ... Low-grade invasive ductal carcinoma may also benefit from staging with FES PET/CT. Early studies (46,47) suggested that FES can be helpful in ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04252859

[18F]Fluoroestradiol-PET/CT Imaging of Invasive Lobular ... Another study evaluating FDG-PET/CT for the diagnosis of primary breast cancer found that the false negative rate for detection of ILC by FDG was 65% (15 of 23 ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12110083/

The Role of [18F]FES PET/CT in Breast Cancer Management This umbrella review aims to evaluate the role of 16α-18F-fluoro-17β-estradiol ([18F]FES) PET/CT as a non-invasive imaging tool for assessing ER ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36919879/

Prospective Pilot Study of 18F-Fluoroestradiol PET/CT in ... The primary aim of this study was to assess the frequency with which sites of histologically proven ILC have abnormal uptake on FES PET/CT.

5. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2821563

16α-18F-Fluoro-17β-Estradiol PET/CT for Staging Estrogen ... Furthermore, FES PET/CT identified true-positive sites of disease in 29 of 30 findings (97%), while SOC detected true-positive sites in 28 of 34 ...

6. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/59/NCT04252859/Prot_SAP_000.pdf

[18F]Fluoroestradiol-PET/CT Imaging of Invasive Lobular ... A Data and Safety Monitoring Committee (DSMC) is established at Huntsman Cancer ... lobular carcinoma of the breast ... safety of 16α-[18F]fluoro-17β-oestradiol.

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2020/212155s000lbl.pdf

CERIANNA™ (fluoroestradiol F 18) - accessdata.fda.gov The uptake of fluoroestradiol F 18 is not specific for breast cancer and may occur in a variety of ER-positive tumors that arise outside of the breast, ...

8. gehealthcare.com gehealthcare.com/products/molecular-imaging-agents/cerianna?srsltid=AfmBOoq0nncpN6q7TGFdpq2t1rC-Xvlh1_jaBy6rax6fPbZpAOW9upkA

Cerianna™ (fluoroestradiol F18) injection Cerianna™ (fluoroestradiol F18) is indicated for use with PET imaging for the detection of ER+ lesions as an adjunct to biopsy in patients with recurrent or ...