(11C)N-Desmethyl-Loperamide as a Marker of P-Glycoprotein Function in Patients With Gliomas
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.
Time Perspective: Prospective
Shivaani Kummar, M.D.
National Cancer Institute (NCI)
United States: Federal Government
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