An Investigation of Brain Tumor Metabolism in Patients Undergoing Surgical Resection

Study ID
STU 062010-157

Cancer Related

Healthy Volunteers

Study Sites

  • Clements University Hospital
  • UT Southwestern Ambulatory Services
  • Zale Lipshy University Hospital
  • Children’s Medical Center (Dallas, Plano, Southlake)
  • Parkland Health & Hospital System

Sarah McNeil

Principal Investigator
Elizabeth Maher, M.D., Ph.D.

Official Title

An Investigation of Brain Tumor Metabolism in Patients Undergoing Surgical Resection

Brief Overview

The study is designed to use infusion of a non-radioactive, naturally occurring isotope of
glucose (13C) in patients undergoing surgical resection for a newly identified brain mass to
obtain the metabolic phenotype of the tumor, and correlate it with the histopathological
diagnosis. In each patient, 13C NMR spectral analysis of tumor extracts will be obtained
after intraoperative infusion of [U-13C]glucose or [1,2-13C]glucose. Whenever feasible,
patients will undergo 3 preoperative imaging studies - 18FDG-PET, diffusion tensor imaging
with 1H-spectroscopy on 3T MR scanner, and ultra high resolution MR imaging on the 7T MR
scanner. The results of these imaging studies will be correlated with the metabolic
phenotype to generate a comprehensive non-invasive view of the tumor with the goal of
identifying infiltrative, metabolically active tumor cells within the brain. In addition, a
comprehensive molecular profile of the tumor will be obtained and enable a
genotype-metabolic phenotype comparative analysis.

Correlative Translational Research The investigators will obtain tumor tissue from each
patient for comprehensive molecular analysis (array CGH, expression profiling, methylation
profiling) which will be correlated with tumor histology, the metabolites identified by
1H-MR spectroscopy and the 13Cglucose metabolic profile. Patients will be followed at
designated time points along their treatment course to obtain information about ongoing
treatment and response, time to tumor progression and overall survival. These parameters
will be used in correlational analysis with the metabolic phenotype.


This study has been expanded to include subjects with primary tumors outside the central
nervous system, including breast cancer, lung cancer, melanoma, renal cell carcinoma,
prostate cancer and colon cancer. Patients with a brain mass identified on brain imaging and
who need surgical resection of the mass will be eligible for this metabolism study. Eligible
study patients will be screened, recruited, and enrolled at UT Southwestern Medical Center
in the Harold C. Simmons Comprehensive Cancer Center, University Hospital - Zale Lipshy and
University Hospital - St. Paul, Children's Medical Center of Dallas as well as at Parkland
Health and Hospital System. We will consent 60 patients, including projected screen failures
and early withdrawals, and anticipate that we will study 25 patients in this clinical
protocol. Once enrolled, patients will undergo a series of preoperative brain imaging
studies including 3T MRI with Diffusion Tensor Imaging (DTI) and 1H-MR spectroscopy, 7T MRI
and a brain 18FDG-PET scan within 7-14 days of the scheduled operation. Of these studies,
only the 3T MRI is standard of care. The DTI and 1H-MR spectroscopy are additional scanning
sequences that are being done for research purposes. Similarly, the 7T MRI and the 18FDG-PET
are being done for research purposes only. On the day of surgery, the patient will have a
peripheral IV started while waiting in the preoperative holding area and a 20% solution of
either [U-13C]glucose and/or [1,2-13C]acetate (to be determined for each individual patient
by the PI) will be infused at a rate of 4g/hr for a maximum of 4 hours. During the infusion
period, 4 timed blood samples will be collected for NMR analysis of 13C-glucose in the
blood. The infusion will continue until the tumor has been resected and samples have been
collected and flash frozen for 13C-NMR spectral analysis and molecular analyses. The
infusion and tumor collection for 13C-NMR analysis is being done for research purposes only.
However, the remainder of the neurosurgical operative and post-operative procedures will be
followed according to standard practice. The patient will be seen 10-14 days after surgery
for a follow up visit at which time an assessment of adverse events will be performed.
Thereafter, every 6 months for 5 years or until death, the patient will be contacted and
data regarding treatment, responses, and tumor progression will be collected for correlative

Participant Eligibility

Inclusion Criteria:

- Male or female, age 18 years or older of any racial or ethnic group

- Spanish-speaking patients will be eligible

- Pre-operative brain MR imaging suggestive of a brain tumor

- Patient able and willing to provide informed consent

- Karnofsky Performance status > 70%

- Negative serum pregnancy test or child bearing potential terminated by surgery,
radiation, menopause or current use of two approved methods of birth control

Exclusion Criteria:

- Patient unable to provide informed consent

- Karnofsky Performance status < 70%

- Patients who are claustrophobic or have other contraindications to MRI, such as
implanted pacemaker device vascular clips, surgical clips, prosthetic valves,
pacemakers, otologic implants

- NYHA class III and IV congestive heart failure

- Psychiatric or addictive disorders that preclude obtaining informed consent

- Unstable angina

- Pregnant or lactating women

- Women of childbearing potential who refuse a pregnancy test (performed during