Advanced PET/MRI Imaging for Breast Cancer

Overseen By Sebastian Eady

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: University of Alabama at Birmingham

Disqualifiers: Pregnancy, Metal implants, others

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

Compensation: Varies

Number of Visits: 10

25 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of the study is to see if using an investigational drug called \[18F\]FMISO with PET/MRI imaging can help monitor and predict the effect of trastuzumab (Herceptin) on chemotherapy in patients diagnosed with advanced HER2 positive breast cancer. This study is for imaging purposes only and is not a treatment study. The results of this study will not change a patient's clinical treatment plan but it may help physicians and researchers better understand how best to treat patients with breast cancer in the future.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. Since this study is for imaging purposes only and not a treatment study, it is likely that you can continue your current medications, but you should confirm with the study team.

What data supports the effectiveness of the treatment [18F]FMISO for breast cancer?

The research suggests that using [18F]FMISO in combination with PET/MRI imaging can provide important information about breast cancer, such as tumor characteristics and potential outcomes. This imaging method might help tailor treatments more precisely for breast cancer patients by offering detailed insights into the disease. ^{1 2 3 4 5}

Is [18F]FMISO safe for use in humans?

Preliminary studies suggest that [18F]FMISO, a tracer used in PET imaging, may be safe for use in humans, as it has been used in clinical applications for imaging hypoxia (low oxygen levels in tissues). However, specific safety data for its use in breast cancer imaging is not detailed in the available research. ^{6 7 8 9 10}

How does the Advanced PET/MRI Imaging treatment for breast cancer differ from other treatments?

The Advanced PET/MRI Imaging treatment for breast cancer is unique because it combines PET and MRI to provide detailed information about tumor biology, including tumor heterogeneity and hypoxia (low oxygen levels in tissues), which can help tailor treatment plans for precision medicine. This approach offers more comprehensive insights compared to traditional imaging methods, potentially improving diagnosis and treatment outcomes. ^{1 6 11 12 13}

Research Team

Jonathan McConathy, MD, PhD

Principal Investigator

University of Alabama at Birmingham

Eligibility Criteria

This trial is for adults aged 18-75 with advanced HER2+ breast cancer, eligible for neoadjuvant therapy and not yet started treatment. Participants must have a tumor identifiable by imaging and an expected lifespan over one year. Pregnant or breastfeeding women, those with MRI contraindications like certain metal implants, tattoos, or weighing over 350 lbs., are excluded.

Inclusion Criteria

I have stage II-III HER2+ breast cancer and haven't started treatment yet.

You must have at least one tumor that can be measured and is larger than 1 cm in diameter.

My breast cancer is HER2 positive based on lab tests.

Exclusion Criteria

Lactating, known or suspected pregnancy. Women with child-bearing potential must have a negative serum β-hCG pregnancy test within 48 hours or a negative urine β-hCG pregnancy test within 48 hours of each PET imaging study

I cannot use a specific dye (ProHance) for MRI scans due to health reasons.

Contraindication for MRI study (e.g. non-removable metal implants or certain tattoos)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Imaging Visits

Participants undergo PET/MRI imaging sessions to monitor the effect of trastuzumab on chemotherapy

Varies by cohort

3-4 visits (in-person)

Follow-up

Participants are monitored for changes in imaging metrics and clinical response

5 years

Every 6 months (medical record review)

Treatment Details

Interventions

• [18F]FMISO

Trial Overview [18F]FMISO PET/MRI imaging is being tested to monitor the response of HER2+ breast cancer to trastuzumab (Herceptin) combined with chemotherapy. This study aims to improve future treatments but won't alter current patient care plans.

Participant Groups

Group I: Herceptin monotherapy cohort Experimental Treatment 1 Intervention

Herceptin monotherapy cohort. Locally advanced HER2+ breast cancer patients receiving neoadjuvant Herceptin monotherapy prior to combination therapy will undergo three contrast-enhanced \[18F\]FMISO PET/MRI scans. Each imaging session will be identical. Imaging session one will be after diagnosis and before beginning monotherapy. Imaging session two will be within 10 days prior to beginning combination therapy with targeted HER2 agents. Imaging session three will be within 10 days prior to beginning the second round of combination therapy with targeted HER2 agents.

Group II: Combination therapy cohort Experimental Treatment 1 Intervention

Locally advanced HER2+ breast cancer patients that receiving neoadjuvant combination therapy including Herceptin will undergo two contrast-enhanced \[18F\]FMISO PET/MRI imaging. Imaging session one will be after diagnosis and before beginning combination therapy. Imaging session two will be within 10 days prior to beginning the second round of combination therapy with targeted HER2 agents.

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Findings from Research

This pilot study involving nine breast cancer patients demonstrated that sequential multiparametric 18[F]FDG/[18F]FMISO PET-MRI can effectively assess tumor heterogeneity and correlate with important prognostic indicators, such as tumor proliferation and recurrence risk.

Strong correlations were found between PET imaging parameters and clinical outcomes, particularly with disease-specific death and metastasis, suggesting that this imaging technique could enhance precision medicine approaches in breast cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential [18F]FDG-[18F]FMISO PET and Multiparametric MRI at 3T for Insights into Breast Cancer Heterogeneity and Correlation with Patient Outcomes: First Clinical Experience. Andrzejewski, P., Wengert, G., Helbich, TH., et al.[2020]

Fluorodeoxyglucose (FDG) PET imaging is crucial for diagnosing, staging, and managing breast cancer, with its sensitivity varying based on tumor size and histology.

FDG PET can significantly alter staging and treatment plans, especially in cases of recurrent disease, and it also provides valuable prognostic and predictive information about the cancer's progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PET Imaging of Breast Cancer: Role in Patient Management. Lebron, L., Greenspan, D., Pandit-Taskar, N.[2016]

PET/MRI, introduced in 2010, combines high-resolution MRI with metabolic PET data, showing high diagnostic value for whole-body cancer staging, particularly in breast cancer.

This imaging modality improves detection of distant metastases and lymph node involvement, potentially allowing for less invasive treatments and reducing the need for extensive surgeries like mastectomy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Role of PET/MR in Breast Cancer? Bruckmann, NM., Morawitz, J., Fendler, WP., et al.[2022]

PET imaging, particularly using FDG PET/CT, is crucial for diagnosing and managing breast cancer, although it has specific clinical indications and limitations.

The review also discusses the emerging role of PET/MRI and the newly approved radiopharmaceutical FES for imaging estrogen receptors, which could enhance the understanding of breast cancer biology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PET Imaging for Breast Cancer. Fowler, AM., Cho, SY.[2021]

PET-MRI is a promising hybrid imaging technology that combines metabolic and functional data from PET with detailed anatomical information from MRI, enhancing the early detection and clinical staging of breast cancer.

Ongoing research into targeted radiopharmaceuticals and automated analysis tools is expected to improve the effectiveness of PET-MRI in diagnosing, staging, and monitoring treatment responses in breast cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical advances in PET-MRI for breast cancer. Fowler, AM., Strigel, RM.[2023]

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 study successfully synthesized two radiotracers, [18F]FMISO and [18F]PM-PBB3, using a new method called 18F-fluoroalkylation, which produced sufficient radioactivity for clinical applications.

Both radiotracers demonstrated appropriate radiochemical yields, with [18F]FMISO achieving a yield of 26% and [18F]PM-PBB3 achieving a yield of 16%, indicating their potential effectiveness for imaging hypoxia and tau pathology in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Automated radiosynthesis of two 18F-labeled tracers containing 3-fluoro-2-hydroxypropyl moiety, [18F]FMISO and [18F]PM-PBB3, via [18F]epifluorohydrin. Ohkubo, T., Kurihara, Y., Ogawa, M., et al.[2021]

In a study of 14 patients with head and neck cancer, FMISO-PET imaging showed a significant decrease in tumor hypoxia during radiotherapy, as indicated by reduced standard uptake values (SUV) and tumor-muscle ratios (TMR).

The majority of patients (11 out of 14) exhibited a change in their hypoxia status towards lower levels after receiving 30Gy of radiation, suggesting that radiotherapy may induce reoxygenation of tumors, which could potentially improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypoxia-imaging with (18)F-Misonidazole and PET: changes of kinetics during radiotherapy of head-and-neck cancer. Eschmann, SM., Paulsen, F., Bedeshem, C., et al.[2022]

The second phase 3 clinical trial of Fluorine-18 Flurpiridaz PET myocardial perfusion imaging (MPI) aims to assess its effectiveness in diagnosing significant coronary artery disease (CAD) in patients suspected of having the condition, using invasive coronary angiography as the gold standard.

This study will also compare the diagnostic efficacy of F-18 Flurpiridaz PET MPI to the traditional Tc-99m-labeled SPECT MPI, particularly in specific subgroups such as females, obese patients, and diabetics, providing a comprehensive evaluation of its performance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing myocardial perfusion in suspected coronary artery disease: rationale and design of the second phase 3, open-label multi-center study of flurpiridaz (F-18) injection for positron emission tomography (PET) imaging. Bourque, JM., Hanson, CA., Agostini, D., et al.[2022]

The fourth synthesis approach for [18F]FMISO, using [18F]epifluorohydrin, achieved a reliable production with a radiochemical yield of 7-12% and a high specific activity of over 400 Ci/mmol in just 1.5 hours.

Preliminary PET studies indicate that [18F]FMISO could be a promising tracer for identifying ischemic but viable heart tissue, suggesting its potential clinical utility in cardiac imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

No-carrier-added synthesis of 3-[18F]fluoro-1-(2-nitro-1-imidazolyl)-2-propanol. A potential PET agent for detecting hypoxic but viable tissues. Hwang, DR., Dence, CS., Bonasera, TA., et al.[2019]

Molecular imaging techniques, such as (18)F-FDG PET/CT and scintimammography, provide functional information that enhances the diagnosis, staging, and monitoring of breast cancer compared to traditional imaging methods.

The development of new radiopharmaceuticals allows for better visualization of specific biomarkers related to breast cancer, which can lead to more targeted therapies and improved patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Nuclear Medicine in diagnosis of breast cancer]. Iakovou, IP., Giannoula, E.[2016]

Positron emission tomography (PET) is becoming an important tool in both the clinical management and research of breast cancer, helping to visualize and understand the disease better.

Current applications primarily use the radiotracer (18)F-fluorodeoxyglucose (FDG), but there is ongoing research into other radiopharmaceuticals that could provide more insights into breast cancer biology and may soon be tested in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current and future use of positron emission tomography (PET) in breast cancer. Mankoff, DA., Eubank, WB.[2018]

The study demonstrated that 18F-FES PET imaging is effective for early prediction of tumor response to endocrine therapy in estrogen receptor-positive breast cancer, showing a strong correlation with tumor growth and ER levels.

In contrast, the other PET tracers, 18F-FDG and 18F-FMISO, did not correlate well with treatment response, highlighting the unique efficacy of 18F-FES in monitoring therapy outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of 18F-FES, 18F-FDG, and 18F-FMISO PET Imaging Probes for Early Prediction and Monitoring of Response to Endocrine Therapy in a Mouse Xenograft Model of ER-Positive Breast Cancer. He, S., Wang, M., Yang, Z., et al.[2018]

References

1. England pubmed.ncbi.nlm.nih.gov

Sequential [18F]FDG-[18F]FMISO PET and Multiparametric MRI at 3T for Insights into Breast Cancer Heterogeneity and Correlation with Patient Outcomes: First Clinical Experience. [2020]

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

PET Imaging of Breast Cancer: Role in Patient Management. [2016]

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

A Role of PET/MR in Breast Cancer? [2022]

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

PET Imaging for Breast Cancer. [2021]

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

Clinical advances in PET-MRI for breast cancer. [2023]

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. England pubmed.ncbi.nlm.nih.gov

Automated radiosynthesis of two 18F-labeled tracers containing 3-fluoro-2-hydroxypropyl moiety, [18F]FMISO and [18F]PM-PBB3, via [18F]epifluorohydrin. [2021]

8. Ireland pubmed.ncbi.nlm.nih.gov

Hypoxia-imaging with (18)F-Misonidazole and PET: changes of kinetics during radiotherapy of head-and-neck cancer. [2022]

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

Assessing myocardial perfusion in suspected coronary artery disease: rationale and design of the second phase 3, open-label multi-center study of flurpiridaz (F-18) injection for positron emission tomography (PET) imaging. [2022]

10. England pubmed.ncbi.nlm.nih.gov

No-carrier-added synthesis of 3-[18F]fluoro-1-(2-nitro-1-imidazolyl)-2-propanol. A potential PET agent for detecting hypoxic but viable tissues. [2019]

11. Greece pubmed.ncbi.nlm.nih.gov

[Nuclear Medicine in diagnosis of breast cancer]. [2016]

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

Current and future use of positron emission tomography (PET) in breast cancer. [2018]

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

Comparison of 18F-FES, 18F-FDG, and 18F-FMISO PET Imaging Probes for Early Prediction and Monitoring of Response to Endocrine Therapy in a Mouse Xenograft Model of ER-Positive Breast Cancer. [2018]