Clinical trial NCT06059690: Biologic Association Between Metabolic Magnetic Resonance-positron Emission Tomograph (MR-PET) and Tissue Measures of Glycolysis in Brain Tumors of Infiltrating Glioblastoma Cells
Official title: Biologic Association Between Metabolic MR-PET and Tissue Measures of Glycolysis in Brain Tumors Visualization, Quantitation, and Targeting of Infiltrating Glioblastoma Cells with PH Sensitive Amine Chemical Exchange Saturation Transfer Magnetic Resonance Imaging-KL2TR001882
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Glioblastoma Multiforme
Glycolytic Index
Epidermal Growth Factor Receptor
Lead sponsor: Jonsson Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: Nitional institute of Health -National Center for Advancing Translational Sciences
First posted: 2023-09-29
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is a single center, prospective surgical study examining the association between imaging measurements and brain tumor tissue features obtained using image-guided biopsies.
Primary purpose: DIAGNOSTIC

Brief summary: 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.

Detailed 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 \&#34;glycolytic index\&#34; 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

Eligibility criteria: 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).

Primary outcomes:
measure: Glycolytic Index
timeFrame: two years
measure: Immunohistochemistry Expression of Glycolytic Molecules
timeFrame: two years
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California at Los Angeles
state: California
Study officials:
affiliation: University of California at Los Angeles
name: Benjamin Ellingson, PhD
role: PRINCIPAL_INVESTIGATOR
References: