REGIONAL INHIBITION OF P-GP ACTIVITY AT THE HUMAN BLOOD-BRAIN BARRIER AS MEASURED BY PET IMAGING
Abstract number :
1.144
Submission category :
5. Human Imaging
Year :
2009
Submission ID :
10054
Source :
www.aesnet.org
Presentation date :
12/4/2009 12:00:00 AM
Published date :
Aug 26, 2009, 08:12 AM
Authors :
Sara Eyal, M. Muzi, A. Ke, J. Link, D. Mankoff, A. Collier and J. Unadkat
Rationale: Regional overexpression of the multidrug resistance transporter P-glycoprotein (P-gp) in epileptic human brain tissue may contribute to pharmacoresistance in epilepsy by lowering target site concentrations of antiepileptic drugs. Using Positron Emission Tomography (PET) imaging, we evaluated the impact of P-gp inhibition by cyclosporine A (CsA) on the distribution of [11C]-verapamil (a P-gp substrate) radioactivity into anatomically distinct brain regions of healthy human volunteers. Methods: Twelve healthy volunteers (6 women and 6 men; age, 20-50 years) were imaged in the absence and the presence of CsA (pseudo steady-state blood CsA concentration 2.1-3.2 μM) after intravenous administration of [11C]-verapamil (0.06-0.13 mCi/kg , <0.12 μg/kg). Regional P-gp activity was expressed as CsA-induced percent change in the ratio of area under the [
Neuroimaging