(11C)dLop as a Marker of P-Glycoprotein Function in Patients With Gliomas
- The blood-brain barrier helps to protect the central nervous system (brain and spinal cord) from harmful toxins, but also prevents potentially useful chemotherapy from reaching brain tumors. The barrier is formed by tight connections between blood vessel cells and molecules found on the surface of brain blood vessels such as Permeability-glycoprotein (Pgp). Pgp may influence whether patients with brain tumors known as gliomas respond to chemotherapy and what side effects they may experience. The compound (11C)N-desmethyl-loperamide ((11C)dLop) reacts to Pgp molecules, and therefore may be used with positron emission tomography (PET) imaging to study the blood brain barrier.
- To study the ability of PET imaging with (11C)dLop to evaluate the blood brain barrier in brain tumor patients.
- Individuals at least 18 years of age who have a brain tumor with characteristics that may be imaged with techniques such as magnetic resonance imaging (MRI) andPET.
- Participants will be screened with a full physical examination and medical history, blood and urine tests, and tumor imaging studies (fluorodeoxyglucose PET and MRI scans with contrast agent).
- The (11C)dLop scan will take 1 hour to perform. Participants will be asked to return for blood and urine tests approximately 24 hours after the PET scan.
- Participants will have followup visits at least every 4 months by repeating a complete history and physical exam and brain MRI. Participants may have repeat scans with (11C)dLop at various points in the course of cancer treatment, but will not have these scans more than twice in a 12-month period.
- Participants will be followed for as long as possible during treatment to see if imaging with (11C)dLop correlates with response to the treatments....
Low Grade Glioma
|Study Design:||Time Perspective: Prospective|
|Official Title:||(11C)N-Desmethyl-Loperamide as a Marker of P-Glycoprotein Function in Patients With Gliomas|
|Study Start Date:||January 2011|
|Estimated Study Completion Date:||September 2012|
A potential impedance to successful glioma chemotherapy is sanctuary for tumor behind the blood brain barrier. P-glycoprotein (Pgp) is an efflux transporter encoded by MDR1 that contributes to the functional regulation of substrates across the cerebrovasular endothelium. Pgp activity in patients with gliomas may influence response to therapy and neurotoxicity. (11C) N-desmethyl-loperamide (11C)dLop) is a radioligand substrate for Pgp, and PET imaging with this molecular marker may provide a non-invasive, in vivo method of examining Pgp function in brain tumor patients.
-To measure the uptake of (11C)N-desmethyl-loperamide ((11C)dLop) using PET imaging as a marker of Pglycoprotein function in patients with intracranial gliomas
- Correlate (11C)dLop PET uptake with perfusion MRI parameters and FDG PET uptake for volumes of interest (VOI) determined by the baseline MRI
- Develop exploratory data for the correlation of (11C)dLop PET imaging with patient outcomes such as response to therapy, survival, and neurotoxicity
- Develop exploratory data for the correlation of (11C)dLop PET imaging with immunohistochemical and molecular genomic assays of MDR1 and Pgp
Patients with predominantly non-enhancing intracranial gliomas will be eligible.
This is a pilot study of (11C)dLop PET imaging in 10 patients with intracranial glioma. Standard uptake values (SUVs) corrected for cerebral blood flow determined by (15O)H20 PET scans will be correlated to DCE-MRI (obtained within prior 2 weeks) and FDG-PET (obtained within prior 4 weeks) to characterize locoregional differences in Pgp function. When available, correlative studies performed on archived tumor tissue acquired immediately subsequent to (11C)dLop scanning will include immunohistochemical assays of Pgp expression, as well as characterization of MDR1 polymorphisms. Patient case histories will be followed longitudinally to make observations about how (11C)dLop imaging may correlate with patient outcomes such as response to therapy, survival, and neurotoxicity.
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Shivaani Kummar, M.D.||National Cancer Institute (NCI)|