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

Sponsor

Jonsson Comprehensive Cancer Center (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06059690

Collaborator

National Center for Advancing Translational Sciences (NCATS) (NIH)

Enrollment

Arm

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Glioblastoma Multiforme Glycolytic Index Epidermal Growth Factor Receptor	Diagnostic Test: pH Measurement of in vivo tissue	Phase 1/Phase 2

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 "glycolytic index" as an experimental GBM imaging biomarker. Prior to bulk tumor resection at the patient's scheduled surgery, pH measurements, using the SoftCell pH probe, will be taken from approximately 3 anatomic sites that have been correlated with the imaging glycolytic index calculation. 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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

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.This is a single center, prospective surgical study examining the association between imaging measurements and brain tumor tissue features obtained using image-guided biopsies.

Masking:

None (Open Label)

Primary Purpose:

Diagnostic

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

Anticipated Study Start Date :

Sep 30, 2023

Anticipated Primary Completion Date :

Sep 30, 2027

Anticipated Study Completion Date :

Sep 30, 2028

Arms and Interventions

Arm	Intervention/Treatment
Other: Arm I en vivo Glycolic Index measurement 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.	Diagnostic Test: pH Measurement of in vivo tissue The investigator will identify multiple (2-5) 5-8mm diameter spherical targets on GI maps for use in stereotactic pH measurement and biopsy acquisition. 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. After the pH probe is removed, the biopsy needle will be placed into the cannula and standard-of-care biopsy tissue will be obtained from the same area where pH measurements were recorded.

Arm

Intervention/Treatment

Other: Arm I en vivo Glycolic Index measurement

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.

Diagnostic Test: pH Measurement of in vivo tissue

The investigator will identify multiple (2-5) 5-8mm diameter spherical targets on GI maps for use in stereotactic pH measurement and biopsy acquisition. 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. After the pH probe is removed, the biopsy needle will be placed into the cannula and standard-of-care biopsy tissue will be obtained from the same area where pH measurements were recorded.

Outcome Measures

Primary Outcome Measures

Glycolytic Index [two years]
The Glycolytic Index (GI), ranging from 0 to ~1, will be quantified using a combination of FDG PET and MRI measurements. GI is defined as elevated glucose uptake (18F-FDG standard uptake with respect to lean body mass, SUL), elevated tumor acidity (MTRasym @ 3ppm or MTRRex), and lower oxygen utilization (relative cerebral metabolic rate of oxygen, rCMRO2, defined as R2' x rCBF/rCBV from oxygen-sensitive SAGE-EPI and DSC perfusion), normalized to cell density (using ADC from diffusion MRI, which is inversely proportional to cell density). Average GI within the biopsy area prior to biopsy will be correlated with MCT expression within the sample based on immunohistochemistry stain density of percentage positive cells as the 1st primary outcome measure."
Immunohistochemistry Expression of Glycolytic Molecules [two years]
MCT expression will be quantified within biopsy samples based on immunohistochemistry stain density of percentage positive cells

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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).

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Jonsson Comprehensive Cancer Center
National Center for Advancing Translational Sciences (NCATS)

Investigators

Principal Investigator: Benjamin Ellingson, PhD, University of California at Los Angeles

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Jonsson Comprehensive Cancer Center

ClinicalTrials.gov Identifier:

NCT06059690

Other Study ID Numbers:

21-002007

First Posted:

Sep 29, 2023

Last Update Posted:

Sep 29, 2023

Last Verified:

Sep 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Yes

Product Manufactured in and Exported from the U.S.:

Additional relevant MeSH terms:

Glioblastoma

Study Results

No Results Posted as of Sep 29, 2023