Metabolic Imaging for Glioblastoma

Overseen By Saima Chaabane

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Jonsson Comprehensive Cancer Center

Disqualifiers: Ferromagnetic devices, Claustrophobia, Renal function, others

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

Compensation: Varies

Number of Visits: 1

50 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 pH Measurement of in vivo tissue for glioblastoma?

Research shows that measuring the acidity (pH) of the tumor environment can help understand tumor growth and response to treatments. For example, studies have used imaging techniques to map pH changes in tumors, which can indicate how well a treatment is working by showing changes in tumor size and cell activity. ^{1 2 3 4 5}

Is metabolic imaging for glioblastoma safe for humans?

The studies primarily focus on imaging techniques in animal models, such as rats, and do not provide direct safety data for humans. However, these imaging methods are noninvasive and involve techniques like MRI, which are generally considered safe in clinical settings. ^{1 3 4 6 7}

How does metabolic imaging differ from other treatments for glioblastoma?

Metabolic imaging for glioblastoma is unique because it uses advanced magnetic resonance techniques to map the acidity (pH) of the tumor environment, which can help guide treatment decisions by identifying areas of the tumor that may be resistant to therapy. This approach is different from standard treatments that typically focus on directly targeting tumor cells without considering the tumor's microenvironment. ^{1 3 4 6 8}

What is the purpose of this trial?

The purpose of this project is to validate a new combined MRI and PET imaging technique as a biomarker or measure of glycolysis in brain tumors. To accomplish this, the investigators propose obtaining image-guided measures of tissue pH and biopsied tissue in tumor areas selected for bulk resection surgery. Investigators will then correlate the imaging measurements with pH, RNA expression, protein expression, and bioenergetics measurements of key glycolytic enzymes.

Research Team

Benjamin Ellingson, PhD

Principal Investigator

University of California at Los Angeles

Eligibility Criteria

This trial is for adults over 18 with new or returning glioblastoma who are scheduled for tumor removal surgery. It's not suitable for those unable to undergo MRI or PET scans, have metal implants that could be hazardous in scans, have severe kidney issues (GFR < 30), or extreme claustrophobia.

Inclusion Criteria

I am older than 18 years.

I have a new or returning glioblastoma and need surgery.

Exclusion Criteria

Patients who cannot obtain an MRI or FDG PET scan with contrast

Those with ferromagnetic implanted devices that might produce a safety hazard (e.g. infusion pumps, pace makers, aneurysm clips, etc.)

My kidney function is severely reduced.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging and Biopsy

Participants undergo FDG-PET scan and MRI, followed by biopsy for glycolytic index measurement and tissue analysis

1-2 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging and biopsy procedures

4 weeks

Treatment Details

Interventions

• pH Measurement of in vivo tissue

Trial Overview The study is testing a novel imaging technique combining MRI and PET to measure glycolysis in brain tumors. Researchers will compare images with actual tissue samples from surgeries to see how well the imaging reflects tumor metabolism.

Participant Groups

Group I: Arm I en vivo Glycolic Index measurement Experimental Treatment 1 Intervention

All biopsies are acquired for standard of care and according to standard of care procedures. A 13-gauge biopsy needle and plastic cannula will be inserted into the region of interest identified on MRI and PET. The biopsy needle will be removed, and the Softcell® pH probe, consisting of a 1.8mm diameter high quality glass tip and 1.6m long wire, will be guided down the cannula and inserted at least 15mm into the tissue. Recordings will be made for 1 minute to stabilize the reading, then the pH probe will be removed from the region of interest and placed into a saline vial for the next biopsy target.

Who Is Running the Clinical Trial?

Jonsson Comprehensive Cancer Center

Lead Sponsor

Trials

373

Recruited

35,200+

Nitional institute of Health -National Center for Advancing Translational Sciences

Collaborator

Trials

1

Recruited

50+

National Center for Advancing Translational Sciences (NCATS)

Collaborator

Trials

394

Recruited

404,000+

Findings from Research

Using a novel imaging technique called BIRDS, researchers were able to map the pH levels within gliomas, revealing that temozolomide treatment not only reduced tumor size and cell proliferation but also normalized the acidic environment of the tumor.

The study found that treated rats showed a significant decrease in the pH difference between the tumor and surrounding tissue, indicating that temozolomide effectively alters the tumor microenvironment, which could enhance therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide arrests glioma growth and normalizes intratumoral extracellular pH. Rao, JU., Coman, D., Walsh, JJ., et al.[2019]

In a study using a murine model of HER2+ breast cancer, researchers found a significant inverse correlation between tumor glucose uptake (measured by 18F-FDG) and extracellular pH, indicating that higher glucose metabolism leads to lower pH levels in tumors.

The combination of PET imaging for glucose uptake and MRI-CEST for pH measurement provides valuable insights into the tumor microenvironment, enhancing our understanding of cancer metabolism and potentially guiding treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In Vivo Imaging of Tumor Metabolism and Acidosis by Combining PET and MRI-CEST pH Imaging. Longo, DL., Bartoli, A., Consolino, L., et al.[2022]

Using a new imaging technique, researchers measured the extracellular pH in glioma tumors in rats, finding that pH levels ranged from 6.5 to 7.5, indicating an acidic tumor microenvironment that supports tumor growth.

Infusing glucose into the tumors significantly lowered the pH and increased lactate levels, but the increase in lactate did not correlate spatially with the decrease in pH, suggesting complex mechanisms of acidity in tumors that are not solely dependent on lactate production.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serial in vivo spectroscopic nuclear magnetic resonance imaging of lactate and extracellular pH in rat gliomas shows redistribution of protons away from sites of glycolysis. Provent, P., Benito, M., Hiba, B., et al.[2013]

This study is the first to noninvasively measure the pH gradient in a rat glioma model, revealing that tumor cells have a higher intracellular pH (pHi) and a lower extracellular pH (pHe) compared to normal brain tissue, which may promote tumor growth.

Understanding the pH gradient in tumors can inform the selection of therapeutic agents, as most treatments are weak acids or bases, potentially enhancing the effectiveness of precision medicine approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Longitudinal Measurements of Intra- and Extracellular pH Gradient in a Rat Model of Glioma. Lim, H., Albatany, M., Martínez-Santiesteban, F., et al.[2019]

A machine learning model using temporal principal component analysis (PCA) of dynamic susceptibility contrast-enhanced (DSC) MRI can effectively estimate tumor acidity in glioblastoma (GBM) patients, based on an analysis of 78 MRI scans from 32 patients.

The study found a strong correlation between the predicted tumor pH values and actual measurements from pH-sensitive imaging, particularly in the peritumoral regions, indicating that this method could enhance our understanding of the tumor microenvironment in GBM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantification of tumor microenvironment acidity in glioblastoma using principal component analysis of dynamic susceptibility contrast enhanced MR imaging. Akbari, H., Kazerooni, AF., Ware, JB., et al.[2021]

The study successfully mapped extracellular pH (pH(e)) in rat brain gliomas using (1)H magnetic resonance spectroscopic imaging, revealing an average pH(e) of 7.084, which is more acidic compared to normal tissue.

The research found that lactate production in gliomas is primarily associated with viable, well-perfused tumor tissue, and that pH(e) does not significantly decrease in areas with higher lactate concentrations, indicating efficient proton clearance in these regions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mapping extracellular pH in rat brain gliomas in vivo by 1H magnetic resonance spectroscopic imaging: comparison with maps of metabolites. García-Martín, ML., Hérigault, G., Rémy, C., et al.[2022]

The study demonstrated that the anticancer drug lonidamine (LND) can induce significant changes in pH-sensitive MRI contrast parameters (AACID and APT*) in brain tumors, allowing for the detection of tumor-selective acidification after treatment.

Using a 9.4-T MRI scanner, researchers found that these changes occurred within 1 hour of LND administration, suggesting that CEST imaging could be a novel method for localizing brain cancer and monitoring its response to chemotherapy without needing additional contrast agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imaging chemical exchange saturation transfer (CEST) effects following tumor-selective acidification using lonidamine. McVicar, N., Li, AX., Meakin, SO., et al.[2015]

The study analyzed intracellular pH in glioblastoma cells using phosphorus-31 MR spectroscopy in 10 patients, revealing a tendency for increased pH levels in glioblastoma compared to healthy brain tissue.

This increase in intracellular pH may serve as an early marker for abnormalities in brain tissue that conventional MRI cannot detect, and could also help assess the effectiveness of chemotherapy treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Intracellular pH measurement in glioblastoma cells: the possibilities of phosphorus-31 MR spectroscopy]. Mertsalova, MP., Pronin, IN., Zakharova, NE., et al.[2020]

References

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

Temozolomide arrests glioma growth and normalizes intratumoral extracellular pH. [2019]

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

In Vivo Imaging of Tumor Metabolism and Acidosis by Combining PET and MRI-CEST pH Imaging. [2022]

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

Serial in vivo spectroscopic nuclear magnetic resonance imaging of lactate and extracellular pH in rat gliomas shows redistribution of protons away from sites of glycolysis. [2013]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Longitudinal Measurements of Intra- and Extracellular pH Gradient in a Rat Model of Glioma. [2019]

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

Quantification of tumor microenvironment acidity in glioblastoma using principal component analysis of dynamic susceptibility contrast enhanced MR imaging. [2021]

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

Mapping extracellular pH in rat brain gliomas in vivo by 1H magnetic resonance spectroscopic imaging: comparison with maps of metabolites. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Imaging chemical exchange saturation transfer (CEST) effects following tumor-selective acidification using lonidamine. [2015]

8. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Intracellular pH measurement in glioblastoma cells: the possibilities of phosphorus-31 MR spectroscopy]. [2020]