18F-FFNP PET/MRI for Breast Cancer

Overseen By Cancer Connect

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: University of Wisconsin, Madison

Must not be taking: Aromatase inhibitors, ER antagonists

Disqualifiers: HER2-positive, Neoadjuvant therapy, Pregnant, 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: 4

53 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

If you are taking hormone replacement therapy or any over-the-counter products or supplements with potential estrogenic effects, you will need to stop taking them during the study until surgery. If you are currently taking aromatase inhibitors or ER antagonists like tamoxifen or raloxifene, you cannot participate in the trial.

What data supports the effectiveness of the drug 18F-FFNP for breast cancer?

Research shows that 18F-FFNP can effectively measure progesterone receptor levels in breast cancer, which helps predict how well a patient might respond to hormone therapies. Studies have demonstrated that 18F-FFNP uptake in tumors correlates with progesterone receptor concentration, indicating its potential as a useful imaging tool for managing breast cancer treatment. ^{1 2 3 4 5}

Is 18F-FFNP PET/MRI safe for use in humans?

The first-in-human study of 18F-FFNP, a compound used in PET imaging for breast cancer, was designed to evaluate its safety and dosimetry (measurement of radiation dose). This suggests that safety assessments have been conducted, although specific safety outcomes are not detailed in the provided abstracts. ^{1 3 4 5 6}

How does the drug 18F-FFNP differ from other treatments for breast cancer?

18F-FFNP is unique because it is a PET imaging agent specifically designed to measure progesterone receptor levels in breast cancer, helping to predict how well a patient might respond to hormone therapies. Unlike traditional treatments that target cancer cells directly, this drug provides detailed information about the tumor's biology, which can guide personalized treatment decisions. ^{1 2 3 5 7}

What is the purpose of this trial?

This clinical trial will investigate an estrogen-regulated parameter as an early measure of endocrine therapy response: progesterone receptor (PR) protein with a progestin-based radioligand, 18F-fluorofuranylnorprogesterone (18F-FFNP). The overall purpose of this research is to test the efficacy of 18F-FFNP PET/MRI for predicting response to presurgical endocrine therapy and to determine the quantitative reliability of 18F-FFNP breast PET/MRI in patients with newly diagnosed PR+ primary breast cancer.

Research Team

Amy M. Fowler

Principal Investigator

UW Carbone Cancer Center

Eligibility Criteria

This trial is for postmenopausal women with newly diagnosed ER+/PR+/HER2- primary breast cancer, who haven't had any neoadjuvant therapy and are planning surgery. They must be able to lie prone for imaging, not have allergies to the study drugs or MRI contrast agents, and can't be on hormone replacement therapy.

Inclusion Criteria

My breast cancer is confirmed by biopsy and is at least 1.0 cm big.

My breast cancer is ER and PR positive but HER2 negative.

I am scheduled for or have had a breast MRI before surgery.

Exclusion Criteria

We need to have slides or tissue samples from your breast biopsy for testing, and if we don't have them, you can't participate in the study.

I have finished all initial treatments for my current cancer.

I don't need sedation for scans but can take mild anxiety medication.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-surgical Treatment

Participants undergo PET/MRI scans before and after 2 weeks of treatment with anastrozole

2 weeks

2 visits (in-person)

Test-Retest

Participants undergo baseline and repeat PET/MRI scans without intervening treatment to determine repeatability

up to 6 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 7 weeks

Long-term Follow-up

Statistical correlation between tumor 18F-FFNP uptake with disease recurrence

up to 5 years

Treatment Details

Interventions

• 18F-fluorofuranylnorprogesterone
• Positron Emissions Tomography / Magnetic Resonance Imaging

Trial Overview The trial tests if a PET/MRI scan using a tracer called 18F-FFNP can predict how well endocrine therapy will work before surgery in breast cancer patients. It also checks the reliability of this method. Participants will undergo blood sampling and receive Gadobenate dimeglumine and Anastrozole.

Participant Groups

Group I: Group 3: Test-Retest Experimental Treatment 3 Interventions

participants will undergo baseline and repeat PET/MRI scans without intervening treatment to determine repeatability

Group II: Group 2: Pre-surgical Treatment Experimental Treatment 4 Interventions

participants will undergo PET/MRI scans before and after 2 weeks treatment with anastrozole

Group III: Group 1: Metabolite Analysis Experimental Treatment 4 Interventions

participants will undergo venous blood sampling during the PET/MRI scan

Who Is Running the Clinical Trial?

University of Wisconsin, Madison

Lead Sponsor

Trials

1,249

Recruited

3,255,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

The study identified 21-fluoro-16 alpha-methyl-19-norprogesterone ([18F]FMNP) as a promising imaging agent for detecting progesterone receptor positive tumors, showing high specificity and minimal binding to other steroid receptors.

In vivo tests in rats demonstrated that [18F]FMNP had significantly higher uptake in uterine and tumor tissues compared to blood, correlating strongly with progesterone receptor concentrations, indicating its potential for effective imaging of progesterone receptor positive neoplasms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical evaluation of a positron emitting progestin ([18F]fluoro-16 alpha-methyl-19-norprogesterone) for imaging progesterone receptor positive tumours with positron emission tomography. Verhagen, A., Luurtsema, G., Pesser, JW., et al.[2019]

PET imaging agents like 16α-[18F]fluoroestradiol (FES), 21-[18F]fluoro-furanyl-nor-progesterone (FFNP), and 16β-[18F]fluoro-5α-dihydrotestosterone (FDHT) can help predict how well patients with breast and prostate cancers will respond to endocrine therapies by visualizing hormone receptors.

The development of these imaging agents reflects a growing understanding of the importance of receptor targeting in cancer treatment, potentially improving clinical management by identifying which patients are more likely to benefit from hormone-based therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PET Imaging Agents (FES, FFNP, and FDHT) for Estrogen, Androgen, and Progesterone Receptors to Improve Management of Breast and Prostate Cancers by Functional Imaging. Katzenellenbogen, JA.[2023]

The study demonstrated that (18)F-FFNP PET is a safe and effective method for imaging progesterone receptors in breast cancer, with no adverse effects reported in 20 patients.

While the maximum uptake of (18)F-FFNP was similar in both PR-positive and PR-negative tumors, the tumor-to-normal breast activity ratio was significantly higher in PR-positive cancers, indicating better imaging potential for these tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of progesterone receptors in breast carcinoma by PET with 21-18F-fluoro-16α,17α-[(R)-(1'-α-furylmethylidene)dioxy]-19-norpregn-4-ene-3,20-dione. Dehdashti, F., Laforest, R., Gao, F., et al.[2021]

A new fluorine-18 labeled analogue of Tanaproget, designed for imaging progesterone receptors (PRs) in breast tumors, shows high uptake in target tissues, indicating its potential effectiveness for positron emission tomography (PET) imaging.

The compound demonstrated excellent selectivity and prolonged retention in tissues, with significant differences in uptake between target tissues and blood, suggesting it could be a valuable tool for guiding endocrine therapy in breast cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of [F-18]fluorine-substituted Tanaproget as a progesterone receptor imaging agent for positron emission tomography. Lee, JH., Zhou, HB., Dence, CS., et al.[2015]

The study demonstrated that 18F-FFNP can effectively measure changes in progesterone receptor (PR) levels in response to estradiol treatment in both human breast cancer cells and tumor xenografts, with significant increases in uptake observed after 48 and 72 hours of treatment.

Importantly, 18F-FFNP showed equivalent binding to both PR isoforms (A and B), indicating its potential as a reliable imaging agent for assessing total PR expression in breast cancer without bias towards specific isoforms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sensitivity and Isoform Specificity of 18F-Fluorofuranylnorprogesterone for Measuring Progesterone Receptor Protein Response to Estradiol Challenge in Breast Cancer. Salem, K., Kumar, M., Yan, Y., et al.[2023]

6 alpha-[18F]fluoroprogesterone shows a relative binding affinity to progesterone receptors (PgR) that is comparable to progesterone, making it a potential imaging agent for PgR-positive breast cancer.

However, in vivo studies indicate that it has low target tissue selectivity and high fat uptake, suggesting that the C-6 position may not be ideal for fluorine-18 labeling in steroid imaging agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

6 alpha-[18F]fluoroprogesterone: synthesis via halofluorination-oxidation, receptor binding and tissue distribution. Choe, YS., Bonasera, TA., Chi, DY., et al.[2019]

Novel PET tracers, such as FES and FFNP, are being developed to measure estrogen and progesterone receptor density in breast cancer, which can help in selecting targeted therapies.

These investigational tracers are advancing towards clinical use and may significantly improve the characterization of breast cancer biology, enhancing the ability to monitor treatment responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel methods and tracers for breast cancer imaging. Linden, HM., Dehdashti, F.[2013]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Preclinical evaluation of a positron emitting progestin ([18F]fluoro-16 alpha-methyl-19-norprogesterone) for imaging progesterone receptor positive tumours with positron emission tomography. [2019]

2. Switzerland pubmed.ncbi.nlm.nih.gov

PET Imaging Agents (FES, FFNP, and FDHT) for Estrogen, Androgen, and Progesterone Receptors to Improve Management of Breast and Prostate Cancers by Functional Imaging. [2023]

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

Assessment of progesterone receptors in breast carcinoma by PET with 21-18F-fluoro-16α,17α-[(R)-(1'-α-furylmethylidene)dioxy]-19-norpregn-4-ene-3,20-dione. [2021]

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

Development of [F-18]fluorine-substituted Tanaproget as a progesterone receptor imaging agent for positron emission tomography. [2015]

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

Sensitivity and Isoform Specificity of 18F-Fluorofuranylnorprogesterone for Measuring Progesterone Receptor Protein Response to Estradiol Challenge in Breast Cancer. [2023]

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

6 alpha-[18F]fluoroprogesterone: synthesis via halofluorination-oxidation, receptor binding and tissue distribution. [2019]

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

Novel methods and tracers for breast cancer imaging. [2013]