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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new imaging method that combines MRI and PET scans to measure how brain tumors process sugar. Researchers aim to determine if these images accurately reflect tumor activity by comparing them to actual tissue samples, including in vivo tissue pH measurements. The study targets individuals with glioblastoma, a type of brain cancer, who are scheduled for surgery. Participants must be able to undergo both MRI and PET scans. As a Phase 1 trial, this research focuses on understanding how this new imaging method functions in people, offering participants the chance to contribute to groundbreaking advancements in brain cancer diagnostics.

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 prior data suggests that this imaging technique is safe for use in brain tumor patients?

Research shows that measuring pH levels in brain tissue is generally safe for humans. Previous studies using similar methods have demonstrated that this can be done without causing harm. For instance, research on animals successfully measured pH levels in tumors without major problems, suggesting that the method is well-tolerated. Additionally, special tools like a pH probe ensure accurate readings while reducing risk. Although this trial remains in the early stages, the technique's previous use in research provides some reassurance about its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it focuses on a novel method for understanding glioblastoma by measuring the pH levels directly within the tumor tissue. Unlike traditional imaging techniques that provide indirect information about tumor activity, this approach uses a Softcell® pH probe to deliver precise, real-time data about the tumor's metabolic state. This technique offers a unique insight into the tumor's environment, which could lead to more personalized and effective treatment strategies. By directly measuring the glycolic index in vivo, researchers hope to better understand the tumor's behavior and tailor treatments accordingly, potentially improving outcomes for patients with glioblastoma.

What evidence suggests that this imaging technique is effective for measuring glycolysis in brain tumors?

This trial will measure the pH level of brain tumor tissue to better understand glioblastoma. Research has shown that glioblastoma cells often create a more acidic environment by relying on a process that breaks down sugar for energy. This acidity can influence tumor cell behavior and growth. By measuring the pH, researchers aim to learn more about the tumor's energy use and growth. This knowledge could lead to new methods for monitoring and treating glioblastoma. ^{6 7 8 9 10}

Who Is on the Research Team?

Benjamin Ellingson, PhD

Principal Investigator

University of California at Los Angeles

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5331044/

Extracellular Proton Concentrations Impacts LN229 ... Extracellular pH impacts glioblastoma tumor cell phenotype and suggests a possible association with cholesterol biosynthesis. (A) LN229 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3047405/

In Vivo Measurement of Regional Brain and Tumor pH Using ... Recalculation of the DMO data for RG-2 gliomas assuming an extracellular space of 30% and that pHe = (pHp + 0.3) yields an average tumor pHi of 7.10 ± 0.11.

3. researchgate.net researchgate.net/figure/extracellular-ph-impacts-ln229-glioblastoma-tumor-cell-biochemical-homeostasis-in-a_fig2_314232405

extracellular ph impacts ln229 glioblastoma tumor cell... Glioblastoma cells with basal and high surface cholesterol levels were incubated in various pH ranges. (a) Intracellular pH (pHi) in different extracellular pH ...

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6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10987279/

Transmembrane pH gradient imaging in rodent glioma models The average pHe values measured using the resampled pHe map in the tumor and normal tissue ROIs were 6.76 ± 0.17 and 7.18 ± 0.04, respectively (Fig. 1M). The pH ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0021925818521645

Acidic Extracellular pH Induces Vascular Endothelial ... Because glioblastomas commonly overexpress VEGF and have a low extracellular pH of 6.78–6.93 (14), they provide an ideal system for examining the mechanisms ...

8. science.org science.org/doi/10.1126/sciadv.adp2840

Positronium image of the human brain in vivo This study presents the in vivo images of positronium lifetime in a human, for a patient with a glioblastoma brain tumor, by using the dedicated Jagiellonian ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12388879/

Improving the Treatment of Brain Gliomas Through Small ... The aim of this study was to develop a Solutol HS-15-based micellar nanoparticle (PSM) to enhance the brain glioma targeting of PTX and reduce ...

10. nature.com nature.com/articles/s41467-017-00598-1

In vivo quantitative imaging of tumor pH by nanosonophore ... As a result, both the pH levels and the hemodynamic properties across the entire tumor can be quantitatively evaluated with high sensitivity and ...