Metabolic Pathway Tracer for Breast Cancer

Recruiting at 1 trial location

Overseen By Coral Omene, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Rutgers, The State University of New Jersey

Disqualifiers: Triple negative, Her2+, Active malignancy, others

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

Compensation: Varies

Number of Visits: 1

Duration: 2-3 hours

16 Participants Needed

Trial Summary

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's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment U-13C-glucose for breast cancer?

Research shows that using 13C6-glucose can help track how cancer cells process glucose, which is important for understanding tumor metabolism. This method has been used to study glucose metabolism in different types of cancer, suggesting it could be useful in assessing breast cancer as well. ^{1 2 3 4 5}

Is U-13C-glucose safe for use in humans?

Research involving U-13C-glucose in mice has shown it can be used safely to trace metabolic processes without causing stress or harm. However, specific safety data for humans is not provided in the available studies. ^{1 2 4 6 7}

How is the treatment U-13C-glucose unique for breast cancer?

U-13C-glucose is unique because it acts as a tracer to study the metabolic pathways in breast cancer cells, helping researchers understand how these cells process glucose differently from normal cells. This approach is different from standard treatments as it focuses on mapping cancer metabolism rather than directly targeting cancer cells for destruction. ^{1 2 8 9 10}

What is the purpose of this trial?

To analyze the metabolic activity of Hormone Receptor Positive (HR+)/Her 2 Negative (Her2-) Breast cancer.

Research Team

Coral Omene, MD, PhD

Principal Investigator

Cancer Institute of New Jersey Rutgers

Eligibility Criteria

This trial is for individuals with HR+/HER2- breast cancer, who haven't had neoadjuvant therapy and are set for curative surgery. They must be willing to provide tissue samples during surgery and not be part of another clinical study or have other active cancers.

Inclusion Criteria

I am a candidate for surgery to remove my cancer and have not had any pre-surgery treatments.

My breast cancer is hormone receptor positive and HER2 negative.

I agree to have small samples of my tumor and normal tissue taken during surgery for research.

Exclusion Criteria

I have another active cancer besides the one being treated.

Is currently enrolled, or will enroll in, a different clinical study in which investigational therapeutic procedures are performed or investigational therapies are administered while participating in this study.

Is of child-bearing potential who has not had a recent negative pregnancy test done outside of this clinical trial (i.e., as part of standard preparation for diagnosis and treatment for her cancer)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive a glucose infusion during routine breast cancer surgery, with tumor biopsy and blood sample collection for metabolic analysis

2-3 hours

1 visit (in-person, intraoperative)

Follow-up

Participants are monitored for metabolic activity analysis using collected samples

3-4 weeks

Treatment Details

Interventions

• U-13C-glucose

Trial Overview The trial studies how hormone receptor-positive, HER2-negative breast cancer cells process sugar by using a special form of glucose called U-13C-glucose during surgical resection of the tumor.

Participant Groups

Group I: Metabolic activity of Hormone Receptor Positive (HR+)/Her 2 Negative (Her2-) Breast cancer Experimental Treatment 1 Intervention

Administration of U-13C-glucose to participants with early-stage HR+/Her2- breast cancer fitting criteria, will be done intraoperatively at the time of resection, as well as blood sample collection. This will allow for in depth evaluation of glycolysis as well as TCA cycle, lipid and amino acid metabolism and comprehensive genomic analyses to complement the metabolic assays that will be done by the Ludwig Institute of Cancer Research. HR+/Her2- breast cancer subtype is chosen for this feasibility pilot study given that metabolic studies have not been done in this subtype of breast cancer and it makes up the majority of breast cancer cases.

Who Is Running the Clinical Trial?

Rutgers, The State University of New Jersey

Lead Sponsor

Trials

471

Recruited

81,700+

Ludwig Institute for Cancer Research

Collaborator

Trials

62

Recruited

1,700+

Findings from Research

The study utilized 2-deoxy-D-[6-13C]glucose to track both the transport and phosphorylation processes in MCF-7 breast cancer cells, providing insights into glucose metabolism in cancer cells.

This method was applied in both in vitro (lab) settings and in vivo (live mice) with subcutaneous tumors, demonstrating its potential for studying cancer metabolism in real biological systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monitoring the transport and phosphorylation of 2-deoxy-D-glucose in tumor cells in vivo and in vitro by 13C nuclear magnetic resonance spectroscopy. Navon, G., Lyon, RC., Kaplan, O., et al.[2019]

A new method for delivering 13C6-glucose through a stress-free liquid diet in rodents allows for significant enrichment of metabolic products, enabling detailed study of various metabolic pathways in mouse tissues over 12 to 48 hours.

This approach revealed that patient-derived lung tumor xenografts utilize glucose from the liver for synthesizing important compounds like glutamate and glutathione, highlighting differences in glucose metabolism between primary tumors and their metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Noninvasive liquid diet delivery of stable isotopes into mouse models for deep metabolic network tracing. Sun, RC., Fan, TW., Deng, P., et al.[2019]

In a study of 146 patients with invasive ductal carcinoma of the breast, a significant positive correlation was found between 18F-FDG uptake and mitochondrial activity, indicating that higher metabolic activity in cancer cells is linked to worse outcomes.

Increased 18F-FDG uptake was associated with a shorter disease-free survival (DFS), suggesting that measuring this uptake can help predict patient prognosis, with a specific cut-off value of 7.76 for pSUVmax identified as significant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reverse Warburg Effect-Related Mitochondrial Activity and 18F-FDG Uptake in Invasive Ductal Carcinoma. Choi, BW., Jeong, YJ., Park, SH., et al.[2022]

The study demonstrated that the monoclonal antibody 213Bi-anti-EGFR-MAb effectively decreased glucose metabolism in bladder cancer cells (EJ28Luc) by reducing the incorporation of carbon from glucose into key amino acids, indicating a strong early treatment response.

In contrast, glioma cells (LN18) did not show the same metabolic response despite being killed by the treatment, suggesting that the effectiveness of the radionuclide therapy may vary between different types of cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diverse metabolic response of cancer cells treated with a 213Bi-anti-EGFR-immunoconjugate. Feuerecker, B., Biechl, P., Seidl, C., et al.[2021]

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]

The newly synthesized compound 6-deoxy-6-fluoro-D-fructose (6FDF) shows promise for improved imaging of breast cancer by targeting overexpressed fructose transporters in cancer cells.

In studies with breast cancer cell lines, 6FDF demonstrated effective transport and accumulation, indicating its potential for use in PET imaging, with further testing planned in mouse models.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis and characterization of 6-deoxy-6-fluoro-D-fructose as a potential compound for imaging breast cancer with PET. Trayner, BJ., Grant, TN., West, FG., et al.[2009]

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]

Using (13)C metabolic flux analysis, researchers identified that [1,2-(13)C(2)]glucose is the most effective tracer for accurately estimating metabolic fluxes in cancer cell metabolism, particularly for glycolysis and the pentose phosphate pathway.

The study also found that [U-(13)C(5)]glutamine is the best tracer for analyzing the tricarboxylic acid (TCA) cycle, providing essential insights for designing more effective metabolic flux analysis experiments in mammalian cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of 13C isotopic tracers for metabolic flux analysis in mammalian cells. Metallo, CM., Walther, JL., Stephanopoulos, G.[2021]

The study used Stable Isotope Resolved Metabolomics to analyze metabolic pathways in different breast cell types, revealing that glycolysis does not correlate with breast cancer cell proliferation, while glutaminolysis is crucial for pyrimidine synthesis across all cell types.

Metabolic differences were observed between in vitro cultures and tumor xenografts of breast cancer cell lines, indicating that the tumor microenvironment significantly influences glucose metabolism, although the inherent metabolic distinctions between the cell lines remained consistent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Probing the metabolic phenotype of breast cancer cells by multiple tracer stable isotope resolved metabolomics. Lane, AN., Tan, J., Wang, Y., et al.[2020]

This study presents a detailed protocol for using 13C-stable isotope tracing to analyze the metabolic processes in HER2+ breast cancer brain metastases in mice, which is crucial for understanding tumor cell dependencies.

The method includes steps for injecting cancer cells to create brain metastases, infusing stable isotopes, and analyzing metabolites, providing a comprehensive approach for future cancer research and potential treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimized protocol for stable isotope tracing and steady-state metabolomics in mouse HER2+ breast cancer brain metastasis. Parida, PK., Marquez-Palencia, M., Kaushik, AK., et al.[2022]

References

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

Monitoring the transport and phosphorylation of 2-deoxy-D-glucose in tumor cells in vivo and in vitro by 13C nuclear magnetic resonance spectroscopy. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Noninvasive liquid diet delivery of stable isotopes into mouse models for deep metabolic network tracing. [2019]

3. Germany pubmed.ncbi.nlm.nih.gov

Reverse Warburg Effect-Related Mitochondrial Activity and 18F-FDG Uptake in Invasive Ductal Carcinoma. [2022]

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

Diverse metabolic response of cancer cells treated with a 213Bi-anti-EGFR-immunoconjugate. [2021]

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. England pubmed.ncbi.nlm.nih.gov

Synthesis and characterization of 6-deoxy-6-fluoro-D-fructose as a potential compound for imaging breast cancer with PET. [2009]

7. 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]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Evaluation of 13C isotopic tracers for metabolic flux analysis in mammalian cells. [2021]

9. Belgium pubmed.ncbi.nlm.nih.gov

Probing the metabolic phenotype of breast cancer cells by multiple tracer stable isotope resolved metabolomics. [2020]

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

Optimized protocol for stable isotope tracing and steady-state metabolomics in mouse HER2+ breast cancer brain metastasis. [2022]