TY - JOUR
T1 - Evaluation of (R)-[11C]verapamil as PET tracer of P-glycoprotein function in the blood-brain barrier
T2 - Kinetics and metabolism in the rat
AU - Luurtsema, Gert
AU - Molthoff, Carla F.M.
AU - Schuit, Robert C.
AU - Windhorst, Albert D.
AU - Lammertsma, Adriaan A.
AU - Franssen, Eric J.F.
PY - 2005/1/1
Y1 - 2005/1/1
N2 - There is evidence that P-glycoprotein (P-gp) in the blood-brain barrier (BBB) may be involved in the aetiology of neurological disorders. For quantification of P-gp function in vivo, (R)-[11C]verapamil can be used as a positron emission tomography (PET) tracer, provided that a mathematical model describing kinetics of uptake and clearance of verapamil is available. To develop and validate such a model, the kinetic profile and metabolism of (R)-[11C]verapamil have to be known. The aim of this study was to investigate the presence of labeled metabolites of [ 11C]verapamil in the plasma and (brain) tissue of Wistar rats. For this purpose, extraction and high-performance liquid chromatography (HPLC) methods were developed. The radioactive metabolites of (R)-[11C] verapamil in the liver were N-dealkylated compounds, O-demethylated compounds and a polar fraction formed from N-demethylation products of (R)-[ 11C]verapamil. Apart from this [11C] polar fraction, other radioactive metabolites of [11C]verapamil were not detected in the brain tissue. Thirty minutes after injection, unmetabolized (R)-[ 11C]verapamil accounted for 47% of radioactivity in the plasma and 69% in the brain. Sixty minutes after injection, unmetabolized (R)-[ 11C] verapamil was 27% and 48% in the plasma and the brain, respectively.
AB - There is evidence that P-glycoprotein (P-gp) in the blood-brain barrier (BBB) may be involved in the aetiology of neurological disorders. For quantification of P-gp function in vivo, (R)-[11C]verapamil can be used as a positron emission tomography (PET) tracer, provided that a mathematical model describing kinetics of uptake and clearance of verapamil is available. To develop and validate such a model, the kinetic profile and metabolism of (R)-[11C]verapamil have to be known. The aim of this study was to investigate the presence of labeled metabolites of [ 11C]verapamil in the plasma and (brain) tissue of Wistar rats. For this purpose, extraction and high-performance liquid chromatography (HPLC) methods were developed. The radioactive metabolites of (R)-[11C] verapamil in the liver were N-dealkylated compounds, O-demethylated compounds and a polar fraction formed from N-demethylation products of (R)-[ 11C]verapamil. Apart from this [11C] polar fraction, other radioactive metabolites of [11C]verapamil were not detected in the brain tissue. Thirty minutes after injection, unmetabolized (R)-[ 11C]verapamil accounted for 47% of radioactivity in the plasma and 69% in the brain. Sixty minutes after injection, unmetabolized (R)-[ 11C] verapamil was 27% and 48% in the plasma and the brain, respectively.
KW - BBB
KW - Metabolites
KW - P-gp
KW - [C]verapamil
UR - http://www.scopus.com/inward/record.url?scp=13244258485&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.nucmedbio.2004.06.007
DO - https://doi.org/10.1016/j.nucmedbio.2004.06.007
M3 - Article
C2 - 15691665
SN - 0969-8051
VL - 32
SP - 87
EP - 93
JO - Nuclear medicine and biology
JF - Nuclear medicine and biology
IS - 1
ER -