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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new imaging method called 4FMFES-PET, which helps doctors observe how breast cancer tumors respond to estrogen, a hormone linked to some cancer growth. This method will be used alongside FDG-PET to enhance understanding and management of advanced breast cancer. The trial seeks individuals diagnosed with advanced ER+ (estrogen receptor-positive) breast cancer, where tumors use estrogen to grow. Participants should have stage 3 or 4 breast cancer and be willing to undergo new imaging tests. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to advancements in breast cancer imaging.

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 prior data suggests that this imaging method is safe for breast cancer patients?

Research has shown that 4FMFES-PET, a new imaging tool for breast cancer, is promising in terms of safety. Studies have found that it provides clear images of estrogen receptors (ERs) in breast cancer, offering better detail and less background interference than current FES-PET imaging. This clarity helps doctors see tumors without extra, confusing signals.

Regarding side effects, no evidence indicates that 4FMFES-PET causes major problems for patients. As this is a phase 2 study, earlier tests have already assessed its safety in humans, deeming it safe enough for more detailed testing. This phase focuses more on its effectiveness, which is encouraging for potential participants.

Overall, current research suggests that 4FMFES-PET is well-tolerated. For specific concerns about risks or side effects, consulting with trial coordinators or a doctor can provide more personalized information. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about 4FMFES-PET imaging because it offers a new way to visualize estrogen receptor-positive (ER+) advanced breast cancers. Unlike the standard FDG-PET scans, which highlight areas of high glucose metabolism, 4FMFES-PET specifically targets and binds to estrogen receptors. This allows for a more precise imaging of ER+ tumors, potentially improving diagnosis and treatment monitoring. By providing clearer insights into tumor behavior and response, this technique could lead to more personalized and effective treatment strategies for patients with ER+ advanced breast cancer.

What evidence suggests that 4FMFES-PET is effective for ER+ breast cancer imaging?

Research has shown that 4FMFES-PET is currently the best imaging tool for assessing estrogen receptor (ER) status in breast cancer. Studies have demonstrated that it provides clearer images and better tumor contrast than the older FES-PET method, making it more reliable for detecting tumors and understanding their ER status. In this trial, participants will undergo 4FMFES-PET imaging at 0, 6, and 18 months. Used alongside FDG-PET, another imaging method, it may help identify breast cancer more accurately. This combination could also predict how well treatments will work for patients with advanced ER+ breast cancer. ^{2 3 4 6 7}

Who Is on the Research Team?

Eric E Turcotte, MD

Principal Investigator

Université de Sherbrooke, Centre de Recherche du CHUS

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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 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]

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]

Citations

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clinicaltrials.gov

clinicaltrials.gov/study/NCT04824014

4FMFES-PET Imaging of ER+ Advanced Breast Cancers

Those results demonstrated that, as of now, 4FMFES-PET is the best imaging modality worldwide for whole-body ER status determination, but further validations ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC6910621/

Improved Estrogen Receptor Assessment by PET Using ...

Conclusion: This phase II study with ER+ breast cancer patients showed that 18F-4FMFES PET achieves a lower nonspecific signal and better tumor contrast than 18 ...

3.

jnm.snmjournals.org

jnm.snmjournals.org/content/50/1/100

18 F-Fluoroestradiol Using Serial Whole-Body PET/CT

4FMFES is a newly developed radiolabeled estradiol analog for PET imaging of estrogen receptors (ERs) that shows improved target-to-background ratios.

4.

withpower.com

withpower.com/trial/phase-3-breast-neoplasms-10-2020-68906

4FMFES-PET Imaging for Breast Cancer

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 ...

5.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/28798032/

Improved Estrogen Receptor Assessment by PET ... - PubMed

This phase II study with ER+ breast cancer patients showed that 18 F-4FMFES PET achieves a lower nonspecific signal and better tumor contrast than 18 F-FES PET.

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clinicaltrials.gov

clinicaltrials.gov/study/NCT04824014?term=AREA%5BBasicSearch%5D(2-methoxyestradiol)&rank=10

4FMFES-PET Imaging of ER+ Advanced Breast Cancers

Our Center designed and evaluated 4-fluoro-11β-methoxy-16α-[18F]fluoroestradiol (4FMFES), a successor PET tracer for ER imaging. Paired comparison during a ...

7.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/23619898/

Assessment of the novel estrogen receptor PET tracer 4- ...

In a tumor-bearing mouse model, 4FMFES achieves better specific tumor uptake and better contrast than FES, making it a promising candidate for ER imaging.