4FMFES-PET Imaging for Breast Cancer

Overseen By Stéphanie Dubreuil

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Centre de recherche du Centre hospitalier universitaire de Sherbrooke

Must not be taking: Anti-ER hormone therapy

Disqualifiers: Pregnancy, Nursing, PET/CT intolerance, 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

Compensation: Varies

Number of Visits: 3

150 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

If you are taking anti-ER hormone therapy like Tamoxifen or Fulvestrant, you will need to stop at least 8 weeks before the imaging. However, you can continue taking aromatase inhibitors and LHRH analogs during the study.

What data supports the effectiveness of the drug 4FMFES-PET for breast cancer?

Research shows that 4FMFES, a new imaging drug, has better imaging performance in detecting estrogen receptors in breast cancer compared to a similar drug, FES, in animal models. This suggests it might be more effective in identifying breast cancer cells that respond to hormone therapy. ^{1 2 3 4 5}

What safety data exists for 4FMFES-PET Imaging in humans?

The safety of 4FMFES has been assessed in healthy women, showing promising results in terms of biodistribution and dosimetry, which are measures of how the substance spreads in the body and the radiation dose absorbed, respectively. Additionally, a phase II clinical trial in breast cancer patients reported encouraging results, indicating that 4FMFES is metabolically stable and provides improved imaging quality with lower background activity compared to a similar agent, suggesting it is generally safe for use in humans. ^{1 3 6 7 8}

How is the drug 4FMFES-PET different from other breast cancer treatments?

4FMFES-PET is a novel imaging drug that provides better tumor contrast and lower background activity compared to the existing 18F-FES PET imaging, making it more effective in identifying estrogen receptor-positive breast cancer lesions. ^{1 3 6 8 9}

What is the purpose of this trial?

Estrogen Receptor (ER) is a crucial prognostic factor and treatment target in breast cancer patients. Knowledge of its status greatly influences the choice of the optimal course of treatment. Pathological evaluations of primary tumor, axillary nodes, and metastases are the only confirmatory approach to ER status determination and are limited to known and accessible sites. However, it is known that many advanced breast cancer patients harbor diseases presenting inter-tumor or temporal ER heterogeneity, as ER expression can vary between tumor foci and can evolve during treatment and at time of recurrence, hence the need for whole-body, non-invasive assessment of ER status. In the last decades, 16α-\[18F\]fluoroestradiol (FES) was developed and evaluated as an ER-targeting positron emission tomography (PET) tracer. FES correlated with ER expression, and recently was shown to be able to predict hormone therapy response. Our Center designed and evaluated 4-fluoro-11β-methoxy-16α-\[18F\]fluoroestradiol (4FMFES), a successor PET tracer for ER imaging. Paired comparison during a phase II clinical trial showed that 4FMFES produced images of better quality, with less overall non-specific signal than FES. It resulted in a significantly improved tumor contrast and tumor detectability using 4FMFES-PET leading to increased diagnosis confidence in early-stage breast cancer compared to FES-PET. Those results demonstrated that, as of now, 4FMFES-PET is the best imaging modality worldwide for whole-body ER status determination, but further validations are necessary to position this method as a standard and essential tool for breast cancer management. Like what was observed for FES-PET, preliminary data suggest that 4FMFES-PET combined with FDG-PET will yield very high sensibility for breast tumor detection, each method being complementary. In continuity with previous work, we seek to expand our clinical knowledge of this high-potential diagnostic imaging through the following main objective: Launch a phase II clinical trial to explore the full potential and benefit of 4FMFES-PET in combination with FDG-PET for advanced ER+ breast cancer patients to demonstrate it is an essential tool for cancer management. This proposed project will focus on 3 specific aims: 1. Compare and complement 4FMFES-PET with FDG-PET and conventional imaging modalities, and evaluate how they improved prognosis and staging of ER+ advanced breast cancer patients; 2. Correlate 4FMFES/FDG uptake and staging with pathological data (histology, receptor status, grade), including distal biopsy metastases sampling; 3. Correlate 4FMFES/FDG uptake and staging with longitudinal outcomes (treatment response, progression-free survival, time-to-relapse) to determine which cohort of patient benefit most from 4FMFES.

Research Team

Eric E Turcotte, MD

Principal Investigator

Université de Sherbrooke, Centre de Recherche du CHUS

Eligibility Criteria

This trial is for adults diagnosed with advanced breast cancer (stage 3 or 4), regardless of gender. Participants must have at least 10% ER-positive tumor cells and be willing to undergo systemic treatment. Pregnant or nursing individuals, those unable to endure a PET/CT scan for 30 minutes, or on certain anti-ER hormone therapies are excluded.

Inclusion Criteria

My breast cancer is at an advanced stage (stage 3 or 4).

My cancer's HER2 status is known.

My tumor is at least 10% estrogen receptor positive.

Exclusion Criteria

You cannot stay still for a PET/CT scan for 30 minutes.

I am on or was on hormone therapy for cancer, but stopped it at least 8 weeks ago if it was Tamoxifen or Fulvestrant.

Patients who are pregnant or nursing

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Imaging

Participants undergo 4FMFES-PET imaging within a 4-week interval of a medically-prescribed FDG-PET

4 weeks

1 visit (in-person)

Follow-up Imaging

4FMFES-PET procedure repeated at 6 and 18 months following the initial scan

18 months

2 visits (in-person)

Long-term Follow-up

Participants are monitored for treatment response, progression-free survival, and time-to-relapse

36 months

Treatment Details

Interventions

• 4FMFES-PET

Trial Overview The study tests the effectiveness of a new PET imaging agent called 4FMFES in combination with FDG-PET. It aims to improve diagnosis confidence by comparing it with conventional imaging and correlating results with pathological data and patient outcomes in advanced ER+ breast cancer management.

Participant Groups

Group I: 4FMFES-PET imaging at 0, 6 and 18 months Experimental Treatment 1 Intervention

Patients burdened with ER+ advanced breast cancers and recruited in the trial will undergo an experimental 4FMFES-PET imaging within a 4-week interval of a medically-prescribed FDG-PET. The 4FMFES-PET procedure will be repeated at 6 and 18 months following the initial scan.

Who Is Running the Clinical Trial?

Centre de recherche du Centre hospitalier universitaire de Sherbrooke

Lead Sponsor

Trials

64

Recruited

33,600+

Canadian Cancer Society (CCS)

Collaborator

Trials

84

Recruited

42,100+

Université de Sherbrooke

Collaborator

Trials

317

Recruited

79,300+

Findings from Research

The novel estrogen receptor PET tracer 4-fluoro-11β-methoxy-16α-[(18)F]fluoroestradiol (4FMFES) demonstrated significantly higher uptake in estrogen receptor-positive (ER+) tumors compared to the traditional tracer 16α-[(18)F]fluoroestradiol (FES) in a study involving tumor-bearing mice.

4FMFES provided better contrast in imaging ER+ tumors, indicating its potential as a more effective tool for estrogen receptor imaging in cancer diagnostics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of the novel estrogen receptor PET tracer 4-fluoro-11β-methoxy-16α-[(18)F]fluoroestradiol (4FMFES) by PET imaging in a breast cancer murine model. Paquette, M., Phoenix, S., Ouellet, R., et al.[2021]

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]

4FMFES, a new radiolabeled estradiol analog for PET imaging, was found to be safe for use in 10 healthy women, with no adverse effects reported during the study.

The imaging showed significant uptake in the uterus, indicating effective targeting of estrogen receptors, and the effective dose of radiation was within acceptable limits, suggesting its potential for clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of human biodistribution and dosimetry of 4-fluoro-11beta-methoxy-16alpha-18F-fluoroestradiol using serial whole-body PET/CT. Beauregard, JM., Croteau, E., Ahmed, N., et al.[2015]

F-FES PET/CT is an effective noninvasive imaging technique for assessing estrogen receptor (ER) expression in breast cancer, showing strong correlation with pathological features and high sensitivity (88.2%) and specificity (87.5%) for distinguishing ER-positive from ER-negative lesions.

The study found significant intratumoral heterogeneity in ER expression, particularly in recurrent or metastatic cases, suggesting that F-FES PET/CT can provide valuable insights for personalized treatment strategies in breast cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Assessment of Estrogen Receptor Status and Its Intratumoral Heterogeneity in Patients With Breast Cancer by Using 18F-Fluoroestradiol PET/CT. Yang, Z., Sun, Y., Xu, X., et al.[2018]

The automated synthesis of 16α-[18F]Fluoroestradiol ([18F]FES) for PET imaging was successfully adapted, producing a high-quality radiopharmaceutical with over 99% purity and a yield of 30-35% in about 75-80 minutes.

This [18F]FES is effective for assessing estrogen receptor expression in breast cancer and monitoring treatment responses, making it suitable for clinical PET studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fully automated radiosynthesis and quality control of estrogen receptor targeting radiopharmaceutical 16α-[18F]fluoroestradiol ([18F]FES) for human breast cancer imaging. Wang, M., Glick-Wilson, BE., Zheng, QH.[2021]

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]

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]

In a phase II clinical trial involving 31 ER-positive breast cancer patients, the novel PET radiotracer 18F-4FMFES demonstrated 2.5 times greater metabolic stability compared to the standard 18F-FES, leading to improved imaging results.

18F-4FMFES provided better tumor contrast and identified 9 more lesions than 18F-FES, resulting in enhanced diagnostic confidence and reduced chances of false-negative results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved Estrogen Receptor Assessment by PET Using the Novel Radiotracer 18F-4FMFES in Estrogen Receptor-Positive Breast Cancer Patients: An Ongoing Phase II Clinical Trial. Paquette, M., Lavallée, É., Phoenix, S., et al.[2020]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Assessment of the novel estrogen receptor PET tracer 4-fluoro-11β-methoxy-16α-[(18)F]fluoroestradiol (4FMFES) by PET imaging in a breast cancer murine model. [2021]

2. Switzerland 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. [2016]

3. United States pubmed.ncbi.nlm.nih.gov

Assessment of human biodistribution and dosimetry of 4-fluoro-11beta-methoxy-16alpha-18F-fluoroestradiol using serial whole-body PET/CT. [2015]

4. United States pubmed.ncbi.nlm.nih.gov

The Assessment of Estrogen Receptor Status and Its Intratumoral Heterogeneity in Patients With Breast Cancer by Using 18F-Fluoroestradiol PET/CT. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Fully automated radiosynthesis and quality control of estrogen receptor targeting radiopharmaceutical 16α-[18F]fluoroestradiol ([18F]FES) for human breast cancer imaging. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Molecular Imaging for Estrogen Receptor-Positive Breast Cancer: Clinical Applications of Whole Body and Dedicated Breast Positron Emission Tomography. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

[18F]fluoroestradiol radiation dosimetry in human PET studies. [2016]

8. United States pubmed.ncbi.nlm.nih.gov

Improved Estrogen Receptor Assessment by PET Using the Novel Radiotracer 18F-4FMFES in Estrogen Receptor-Positive Breast Cancer Patients: An Ongoing Phase II Clinical Trial. [2020]

9. United States pubmed.ncbi.nlm.nih.gov

PET imaging of estrogen receptors as a diagnostic tool for breast cancer patients presenting with a clinical dilemma. [2016]