Sanabria-Bohorquez-SM; Labar-D; Leveque-P; Bol-A; De-Volder-AG; Michel-C;
Veraart-C
RP: Veraart, C;
Univ Catholique Louvain, Neural Rehabil Engn Lab GREN5446, B-1200 Brussels, Belgium; Catholic Univ Louvain, Positron Emiss Tomog Lab, Brussels, Belgium; Catholic Univ Louvain, Pharmaceut Chem & Radiopharmacol Unit, Brussels, Belgium
EUROPEAN-JOURNAL-OF-NUCLEAR-MEDICINE. NOV 2000; 27 (11) : 1674-1683
AB: In this work, a mathematical correction for metabolites has
been validated which estimates the relative amount of [C-11]flumazenil
([C-11]FMZ) in the total plasma curve from the tissue kinetic data without
the need for direct metabolite measurement in blood plasma samples. Kinetic
data were obtained using a 90-min three-injection protocol on five normal
volunteers. First, the relative amount of [C-11]FMZ in plasma was modelled
by a two-parameter exponential function. The parameters were estimated
either directly by fitting this model to the blood plasma metabolite measurements,
or indirectly from the simultaneous fitting of tissue time activity curves
from several brain regions with a non-linear FMZ kinetic model. Second,
the direct and indirect metabolite corrections were fixed and the FMZ compartmental
parameters were determined on a regional basis in the brain. The validation
was performed by comparing the regional values of benzodiazepine receptor
density B-max and equilibrium dissociation constant K-d Obtained with the
direct metabolite correction with those values obtained with the indirect
correction. For B-max the correlation coefficient r(2) was above 0.97 for
all subjects and the slope values of the linear regression were within
the interval [0.97, 1.2]. For K-d, r(2) was above 0.96, and the slope values
of the linear regression were within the interval [0.99, 1.1]. Simulation
studies were performed in order to evaluate whether this metabolite correction
method could be used in a clinical protocol where only a single [C-11]FMZ
injection and a linear compartmental model are used. The resulting [C-11]FMZ
distribution volume estimates were found to be linearly correlated with
the true values, with r(2) = 1.0 and a slope value of 1.1. The mathematical
metabolite correction proved to be a feasible and reliable method to estimate
the relative amount of [C-11]FMZ in plasma and the compartmental model
parameters for time-injection protocols. Although validation with real
data is necessary, simulation results suggest that our analysis method
may also be applied to single-injection protocols.