Biologic Association Between Metabolic Magnetic Resonance-positron Emission Tomograph (MR-PET) and Tissue Measures of Glycolysis in Brain Tumors of Infiltrating Glioblastoma Cells

Jonsson Comprehensive Cancer Center

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Glioblastoma Multiforme; Epidermal Growth Factor Receptor; Glycolytic Index

Treatments: Diagnostic Test: pH Measurement of in vivo tissue

Study type: Interventional

Funder types: Other

Identifiers

NCT06059690

21-002007

Details and patient eligibility

About

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.

Full description

Patients who are scheduled for resection of glioblastoma multiforme (GBM) as part of standard care will be invited to take part in the study. All patients will undergo FDG-PET scan for the study using standard clinical imaging techniques, along with standard brain MRI plus up to approximately 15 minutes of investigational MR imaging sequences to permit calculation of "glycolytic index" as an experimental GBM imaging biomarker. Following pH measurements, the patient's clinical biopsy/tumor resection will take place as planned for clinical care. Tissue samples resected during the clinical procedure will be obtained and processed using immunohistochemistry techniques for further assessments, including RNA sequencing and bioenergetics analysis.

The current study will investigate the central hypothesis that biopsied tumor tissue undergoing high levels of glycolysis via RNA expression, protein expression, and bioenergetics analyses can be reliably detected, correlates with direct measure of tissue pH, and is strongly associated with a "glycolytic index" created by combining 18F-FDG PET, amine CEST-SAGE-EPI, perfusion MRI and diffusion MRI. In addition, the investigators will investigate whether metabolic differences identified from this imaging modality may identify infiltrating non-enhancing tumor cells.

FDG: 18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose CEST: chemical exchange saturation transfer SAGE: spin and gradient echo EPI: echo planar imaging IHC: immuno-histochemical rCBF: regional cerebral blood flow rCBV: relative cerebral volume DSC: dynamic susceptibility contrast ADC: apparent diffusion coefficient MCT: Monocarboxylate transporters

Enrollment: 50 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age > 18
• Patients with newly diagnosed or recurrent glioblastoma clinically indicated for resective 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.) will be excluded from the study along with subjects with severe claustrophobia or who have severely compromised renal function (GFR < 30).

Trial design

Primary purpose: Diagnostic

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

50 participants in 1 patient group

Arm I en vivo Glycolic Index measurement

Other group

Description:

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.

Treatment:

Diagnostic Test: pH Measurement of in vivo tissue