1: Eur J Nucl Med Mol Imaging. 2003 Dec;30(12):1630-6. Epub 2003 Sep 06. 

Quantification of human brain benzodiazepine receptors using
[(18)F]fluoroethylflumazenil: a first report in volunteers and epileptic
patients.

Leveque P, Sanabria-Bohorquez S, Bol A, De Volder A, Labar D, Van Rijckevorsel
K, Gallez B.

Unite de tomographie par positrons, Universite catholique de Louvain,
Louvain-la-Neuve, Belgium.

Fluorine-18 fluoroethylflumazenil ([(18)F]FEF) is a tracer for central
benzodiazepine (BZ) receptors which is proposed as an alternative to carbon-11
flumazenil for in vivo imaging using positron emission tomography (PET) in
humans. In this study, [(18)F]FEF kinetic data were acquired using a 60-min
two-injection protocol on three normal subjects and two patients suffering from
mesiotemporal epilepsy as demonstrated by abnormal magnetic resonance imaging
and [(18)F]fluorodeoxyglucose positron emission tomography. First, a tracer
bolus injection was performed and [(18)F]FEF rapidly distributed in the brain
according to the known BZ receptor distribution. Thirty minutes later a
displacement injection of 0.01 mg/kg of unlabelled flumazenil was performed.
Activity was rapidly displaced from all BZ receptor regions demonstrating the
specific binding of [(18)F]FEF. No displacement was observed in the pons. Plasma
input function was obtained from arterial blood sampling, and metabolite
analysis was performed by high-performance liquid chromatography. Metabolite
quantification revealed a fast decrease in tracer plasma concentration, such
that at 5 min post injection about 70% of the total radioactivity in plasma
corresponded to [(18)F]FEF, reaching 24% at 30 min post injection. The
interactions between [(18)F]FEF and BZ receptors were described using linear
compartmental models with plasma input and reference tissue approaches. Binding
potential values were in agreement with the known distribution of BZ receptors
in human brain. Finally, in two patients with mesiotemporal sclerosis, reduced
uptake of [(18)F]FEF was clearly observed in the implicated left hippocampus.

PMID: 13680197 [PubMed - in process]