FFNP-PET/MR Imaging for Breast Cancer

Overseen By Gemma Gliori, MS

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: University of Wisconsin, Madison

Must not be taking: Chemotherapy, Endocrine therapy

Disqualifiers: Pregnancy, Breast expanders, Liver failure, 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: 1

Duration: 1 day

20 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently undergoing or have recently received chemotherapy or endocrine therapy within the last 6 months.

What data supports the effectiveness of the drug [18F]Fluorofuranylnorprogesterone (FFNP) for breast cancer?

Research shows that FFNP can effectively image progesterone receptors in breast cancer, which helps predict how well patients will respond to hormone therapy. In a study, an increase in FFNP uptake after an estradiol challenge was highly predictive of positive response to endocrine therapy in women with estrogen receptor-positive breast cancer. ^{1 2 3 4 5}

Is FFNP-PET/MR Imaging for Breast Cancer safe for humans?

The first-in-human study of FFNP (a type of imaging agent) for breast cancer showed it was safe for use in humans, focusing on its ability to image progesterone receptors in tumors. ^{1 2 3 4 6}

How does the drug FFNP-PET/MR Imaging for Breast Cancer differ from other treatments?

FFNP-PET/MR Imaging is unique because it uses a special tracer, 21-(18)F-fluoro-16α,17α-[(R)-(1'-α-furylmethylidene)dioxy]-19-norpregn-4-ene-3,20-dione, to specifically image progesterone receptors in breast cancer tumors. This approach helps in assessing the presence of these receptors, which can guide the selection of targeted endocrine therapies, unlike traditional imaging methods that do not provide this specific molecular information. ^{1 2 3 4 7}

What is the purpose of this trial?

The goal of this research is to test the accuracy of PET/MRI imaging with 18F-fluorofuranylnorprogesterone (FFNP) for measuring progesterone receptor (PR) expression in patients with invasive breast cancer. The hypothesis is that FFNP SUVmax from PET/MRI will correlate well against the semi-quantitative PR immunohistochemistry score.

Research Team

Amy Fowler, MD, PhD

Principal Investigator

University of Wisconsin, Madison

Eligibility Criteria

This trial is for women over 18 with invasive breast cancer that's at least 1 cm big, as seen on any imaging test. They must be getting a diagnostic MRI and have PR-positive or PR-negative breast cancer. It's not for those who can't lie prone for the scan, have liver failure, MRI contraindications like claustrophobia or certain implants, allergies to FFNP or gadolinium contrast agents, recent neoadjuvant therapy/surgery/radiation, are pregnant/lactating, exceed the scanner size limit, or have breast expanders.

Inclusion Criteria

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

My breast cancer is confirmed by biopsy to be either PR-positive or PR-negative.

I am a woman aged 18 or older.

Exclusion Criteria

I cannot lie on my stomach for 30 minutes.

Your body is too big to fit inside the PET/MRI scanner.

You have breast expanders.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo FFNP PET/MRI imaging to assess PR+ breast malignancies

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging

4 weeks

Treatment Details

Interventions

• [18F]Fluorofuranylnorprogesterone (FFNP)

Trial Overview The study tests if PET/MRI scans using a tracer called [18F]Fluorofuranylnorprogesterone (FFNP) can accurately measure progesterone receptor levels in invasive breast cancer. The idea is that the maximum signal from FFNP on the scan will match up well with lab scores of hormone receptor status.

Participant Groups

Group I: FFNP PET/MRI Experimental Treatment 1 Intervention

18F-Fluorofuranylnorprogesterone (FFNP) administration for PET/MRI imaging to assess biopsy-proven primary PR+ breast malignancies.

Who Is Running the Clinical Trial?

University of Wisconsin, Madison

Lead Sponsor

Trials

1,249

Recruited

3,255,000+

National Center for Advancing Translational Sciences (NCATS)

Collaborator

Trials

394

Recruited

404,000+

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]

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]

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]

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]

In a study of 43 postmenopausal women with advanced ER+ breast cancer, a one-day estradiol challenge significantly increased tumor uptake of the progestin analog FFNP in those who responded to endocrine therapy, indicating a strong predictive relationship (100% sensitivity and specificity).

The study found that responders to endocrine therapy not only showed increased FFNP uptake but also experienced significantly longer survival compared to nonresponders, highlighting the potential of this method to guide treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of PET-based estradiol-challenge test for breast cancer progesterone receptors with response to endocrine therapy. Dehdashti, F., Wu, N., Ma, CX., et al.[2021]

Positron emission tomography/computed tomography (PET/CT) is a rapidly growing imaging technique in cancer management, but the commonly used radiotracer [(18)F]fluorodeoxyglucose (FDG) is not specific for malignant disease, highlighting the need for more tumor-specific PET radiopharmaceuticals.

Over the past 15 years, various alternative (18)F-labeled radiotracers have been developed and evaluated, which may provide better characterization of tumor biology, emphasizing the importance of regulatory compliance and safety in their clinical application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

(18)F-labeled positron emission tomographic radiopharmaceuticals in oncology: an overview of radiochemistry and mechanisms of tumor localization. Vallabhajosula, S.[2022]

The synthesized compound 21-[18F]fluoro-16 alpha-ethyl-19-norprogesterone (FENP) shows high affinity for the progesterone receptor and can be produced in a two-step synthesis with a yield of 4-30% within 40 minutes after [18F]fluoride ion production.

In vivo studies in estrogen-primed rats reveal that [18F]FENP has highly selective uptake in the uterus, indicating its potential for imaging progestin target tissues and receptor-rich tumors, such as breast tumors, using positron emission tomography.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

21-[18F]fluoro-16 alpha-ethyl-19-norprogesterone: synthesis and target tissue selective uptake of a progestin receptor based radiotracer for positron emission tomography. Pomper, MG., Katzenellenbogen, JA., Welch, MJ., et al.[2019]

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. 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]

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

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

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. England pubmed.ncbi.nlm.nih.gov

Association of PET-based estradiol-challenge test for breast cancer progesterone receptors with response to endocrine therapy. [2021]

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

(18)F-labeled positron emission tomographic radiopharmaceuticals in oncology: an overview of radiochemistry and mechanisms of tumor localization. [2022]

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

21-[18F]fluoro-16 alpha-ethyl-19-norprogesterone: synthesis and target tissue selective uptake of a progestin receptor based radiotracer for positron emission tomography. [2019]