Advanced PET/MR Imaging for Breast Cancer

Overseen By Anna Sorace, PhD

Age: 18+

Sex: Female

Trial Phase: Phase 1 & 2

Sponsor: University of Alabama at Birmingham

Must be taking: HER2-targeted treatment

Disqualifiers: Pregnancy, Uncontrolled disorders, Obesity, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

20 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of the study is to see if a new group of imaging tests can help identify response to stage IV HER2+ breast cancer before treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment 2-deoxy-2-[18F]fluoro-D-glucose for breast cancer?

Research shows that 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) can provide important information about breast cancer tumors, such as their glucose metabolism, which is linked to patient outcomes like survival and risk of metastasis. This imaging technique helps doctors understand the tumor better and tailor treatments for breast cancer patients. ^{1 2 3 4 5}

Is 2-[18F]-FDG safe for use in humans?

2-[18F]-FDG, used in PET imaging, is generally considered safe for humans. It is rapidly excreted in urine and does not interfere with normal glucose metabolism. The radiation dose from 2-[18F]-FDG is low, with a small risk of radiation-induced cancer, estimated at 1 in 2000. ^{1 6 7 8 9}

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

Advanced PET/MR Imaging for breast cancer is unique because it combines PET and MRI technologies to provide detailed images of both the metabolic activity and the structure of tumors, which can help in detecting skeletal metastases and understanding tumor heterogeneity. This approach offers more comprehensive diagnostic information compared to traditional imaging methods, potentially leading to more personalized treatment plans. ^{2 10 11 12 13}

Research Team

Anna Sorace, PhD

Principal Investigator

University of Alabama at Birmingham

Eligibility Criteria

This trial is for adults aged 18-75 with Stage IV HER2+ breast cancer who haven't started a new HER2-targeted therapy. They must have measurable disease, an expected lifespan over six months, and can be estrogen/progesterone receptor positive or negative. Excluded are those with certain medical conditions, metal in their body incompatible with MRIs, pregnant/breastfeeding women, and anyone unable to lie still for imaging.

Inclusion Criteria

I am between 18 and 75 years old.

I have HER2+ metastatic breast cancer.

Patients must have one tumor that can be measured according to specific guidelines.

Exclusion Criteria

I have a serious health condition that could affect my participation in the study.

I cannot stay still for an hour on an imaging table.

I have metastatic breast cancer, am HER2 positive, and have started HER2-targeted treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Imaging

Baseline imaging using PET/MRI to establish initial metrics

1 week

1 visit (in-person)

Treatment Monitoring

Participants undergo imaging up to three times during therapy to monitor response

6 months

3 visits (in-person)

Follow-up

Participants are monitored for changes in imaging metrics and disease progression

5 years

Treatment Details

Interventions

• [18F]-FDG

Trial Overview The study tests whether advanced PET/MR imaging using [18F]-FDG can detect early responses to targeted therapy in patients with advanced-stage HER2+ breast cancer before treatment begins.

Participant Groups

Group I: [18F]-Fluorodeoxyglucose (FDG) PET/ MRI Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Findings from Research

The study demonstrated that 18F-FDG can effectively induce cell death in breast cancer tumors, with small tumors showing apoptotic cell death and larger tumors exhibiting necrosis, without damaging normal mammary tissue.

Doses of 18F-FDG up to 5 mCi were found to be non-radiotoxic to healthy organs, suggesting that it could be a safe and effective radiomolecular therapy for breast cancer patients, particularly in cases where standard treatments fail.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Positron emission tomography agent 2-deoxy-2-[18F]fluoro-D-glucose has a therapeutic potential in breast cancer. Moadel, RM., Nguyen, AV., Lin, EY., et al.[2018]

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]

In a study of 466 women with ER-positive, HER2-negative breast cancer, higher levels of 18F-fluorodeoxyglucose metabolism (measured by maximum standardized uptake value) were associated with significantly lower distant relapse-free survival (DRFS) and overall survival (OS).

Patients in the low tertile of SUV had an 8-year DRFS rate of 90.7%, while those in the middle and high tertiles had a rate of only 73.7%, indicating that PET/CT imaging can be a valuable tool for assessing the risk of metastasis and mortality in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association between tumor 18F-fluorodeoxyglucose metabolism and survival in women with estrogen receptor-positive, HER2-negative breast cancer. Chae, SY., Park, SH., Lee, HS., et al.[2022]

In a study of 179 breast cancer patients, FDG PET/CT scans were able to identify disease recurrence in 63.7% of cases, indicating its effectiveness as a diagnostic tool.

Patients with PET/CT evidence of recurrence had significantly shorter overall survival compared to those without recurrence, highlighting the prognostic value of FDG PET/CT in both luminal A and B breast cancer subtypes, regardless of tumor marker levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact on the long-term prognosis of FDG PET/CT in luminal-A and luminal-B breast cancer. Urso, L., Quartuccio, N., Caracciolo, M., et al.[2023]

In a study of 70 patients with primary breast carcinoma, the differential absorption ratio (DAR) calculated from FDG PET scans was found to be a significant prognostic indicator, with higher DAR values correlating to worse overall and relapse-free survival rates.

Patients with a high DAR (≥3.0) had significantly poorer prognoses compared to those with a low DAR (<3.0), highlighting the potential of FDG PET as a tool for predicting outcomes in breast cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predicting the prognoses of breast carcinoma patients with positron emission tomography using 2-deoxy-2-fluoro[18F]-D-glucose. Oshida, M., Uno, K., Suzuki, M., et al.[2022]

2-Deoxy-2-[(18)F]fluoro-D-glucose (2-(18)FDG) is a highly effective PET tracer used in various medical fields, including oncology and cardiology, due to its ability to reflect glucose metabolism and disease progression.

Several new radiofluorinated carbohydrates, such as 2-deoxy-2-[(18)F]fluoro-D-galactose and 6-deoxy-6-[(18)F]fluoro-D-fructose, show promise for diagnosing specific conditions like liver cancer and breast cancer, indicating potential for further development in medical imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiofluorinated carbohydrates for positron emission tomography. Mun, J.[2019]

The synthesis of 2-deoxy-2-[18F]fluoro-D-glucopyranosyl [18F]fluoride was achieved with a radiochemical yield of approximately 28% in a total synthesis time of 70 minutes, indicating a relatively efficient process for producing this compound.

Biodistribution studies in mice showed that the compound defluorinates in vivo to produce 2-deoxy-2-[18F]fluoro-D-glucose and [18F]fluoride, suggesting potential applications in imaging or therapeutic interventions involving glucose metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis and biodistribution of 2-deoxy-2-[18F]fluoro-D-glucopyranosyl [18F]fluoride in mice. Shiue, CY., Arnett, CD., Wolf, AP.[2019]

6-[(18)F]FDF, a new PET radiotracer, shows promise for imaging GLUT5 expression in breast cancer, demonstrating significant uptake in breast cancer cells independent of glucose levels, which could improve detection compared to traditional [(18)F]FDG.

In vivo studies revealed that 6-[(18)F]FDF accumulates effectively in EMT-6 tumors, suggesting its potential as a more specific imaging agent for certain breast cancers, particularly those expressing GLUT5 and ketohexokinase.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiopharmacological evaluation of 6-deoxy-6-[18F]fluoro-D-fructose as a radiotracer for PET imaging of GLUT5 in breast cancer. Wuest, M., Trayner, BJ., Grant, TN., et al.[2016]

2-[18F]-FDG is a safe and effective PET radiopharmaceutical used for imaging, with a low dose of 185 to 370 MBq per patient, resulting in a total effective radiation dose of 7.8 to 10 mSv, which is considered low risk for radiation-induced malignancy.

The compound does not interfere with normal glucose metabolism, is retained in cells for several hours after uptake, and is rapidly excreted, making it a reliable tool for diagnostic imaging without significant toxicological concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Toxicity and radiation dosage of 2-(18F)-2-desoxy-D-glucose in positron emission tomography]. Ruhlmann, J., Oehr, P., Bender, H., et al.[2013]

In a study involving 74 patients with advanced breast and prostate cancers, the combined Na[18F]F/[18F]FDG PET/MRI technique detected significantly more skeletal lesions (140) compared to the standard [99mTc]MDP whole-body bone scintigraphy (81 lesions).

The PET/MRI approach also identified extra-skeletal lesions in 19 patients, suggesting it may provide a more comprehensive assessment of disease spread compared to traditional imaging methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simultaneous PET/MRI in the Evaluation of Breast and Prostate Cancer Using Combined Na[18F] F and [18F]FDG: a Focus on Skeletal Lesions. Sonni, I., Minamimoto, R., Baratto, L., et al.[2021]

In a study of 45 breast cancer patients, (18)F-FDG PET/CT demonstrated slightly higher accuracy (86.7%) compared to (18)F-NaF PET/CT (84.4%) for detecting bone metastases, indicating its reliability as a diagnostic tool.

While (18)F-FDG PET/CT was generally more effective, (18)F-NaF PET/CT showed superior sensitivity in specific cases, such as detecting sclerotic lesions and in patients with high suspicion of relapse, leading to changes in management for 6.6% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparisons between glucose analogue 2-deoxy-2-((18)F)fluoro-D-glucose and (18)F-sodium fluoride positron emission tomography/computed tomography in breast cancer patients with bone lesions. Capitanio, S., Bongioanni, F., Piccardo, A., et al.[2020]

In a study of 100 patients with FDG-avid lymphomas, the analysis of [18F]-FDG-PET/MR data revealed that standardized uptake values (SUVs) and apparent diffusion coefficients (ADCs) are independent biomarkers, indicating they provide different information about the disease.

A significant correlation between ADCmean and SUVmean was found specifically in follicular lymphoma, suggesting that while SUVs and ADCs generally do not correlate, they may have a moderate relationship in this particular subtype.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Correlation between glycolytic activity on [18F]-FDG-PET and cell density on diffusion-weighted MRI in lymphoma at staging. Giraudo, C., Karanikas, G., Weber, M., et al.[2019]

FDG-PET/CT is an effective imaging tool that combines metabolic and anatomical data, enhancing the diagnosis and management of breast cancer and other tumors in a single session.

This imaging technique is valuable for various stages of cancer management, including diagnosis, staging, treatment response assessment, and evaluating metastatic disease, although it also has some limitations that need to be considered.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Present and future role of FDG-PET/CT imaging in the management of breast cancer. Kitajima, K., Miyoshi, Y.[2022]

References

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

Positron emission tomography agent 2-deoxy-2-[18F]fluoro-D-glucose has a therapeutic potential in breast cancer. [2018]

2. 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]

3. England pubmed.ncbi.nlm.nih.gov

Association between tumor 18F-fluorodeoxyglucose metabolism and survival in women with estrogen receptor-positive, HER2-negative breast cancer. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Impact on the long-term prognosis of FDG PET/CT in luminal-A and luminal-B breast cancer. [2023]

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

Predicting the prognoses of breast carcinoma patients with positron emission tomography using 2-deoxy-2-fluoro[18F]-D-glucose. [2022]

6. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Radiofluorinated carbohydrates for positron emission tomography. [2019]

7. Germany pubmed.ncbi.nlm.nih.gov

Synthesis and biodistribution of 2-deoxy-2-[18F]fluoro-D-glucopyranosyl [18F]fluoride in mice. [2019]

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

Radiopharmacological evaluation of 6-deoxy-6-[18F]fluoro-D-fructose as a radiotracer for PET imaging of GLUT5 in breast cancer. [2016]

9. Austria pubmed.ncbi.nlm.nih.gov

[Toxicity and radiation dosage of 2-(18F)-2-desoxy-D-glucose in positron emission tomography]. [2013]

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

Simultaneous PET/MRI in the Evaluation of Breast and Prostate Cancer Using Combined Na[18F] F and [18F]FDG: a Focus on Skeletal Lesions. [2021]

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

Comparisons between glucose analogue 2-deoxy-2-((18)F)fluoro-D-glucose and (18)F-sodium fluoride positron emission tomography/computed tomography in breast cancer patients with bone lesions. [2020]

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

Correlation between glycolytic activity on [18F]-FDG-PET and cell density on diffusion-weighted MRI in lymphoma at staging. [2019]

13. Japan pubmed.ncbi.nlm.nih.gov

Present and future role of FDG-PET/CT imaging in the management of breast cancer. [2022]