PMID: 16644748Apr 29, 2006Paper

SPECT quantification of benzodiazepine receptor concentration using a dual-ligand approach

Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine
Philippe MilletV Ibáñez

Abstract

The distribution of benzodiazepine receptors in the human brain has been widely studied with SPECT using (123)I-iomazenil and semiquantitative approaches, but these methods do not allow quantification of the total receptor site concentration available for binding (B'(max)) and of the apparent equilibrium dissociation constant (K(d)/V(R)). One of the major obstacles to full quantitative studies is that pharmacologic effects preclude the administration to humans of the high doses of iomazenil required to displace the labeled ligand from the receptors. In this study, we applied a dual-ligand protocol using the unlabeled ligand flumazenil, which lacks pharmacologic effects, to quantify all binding parameters of the benzodiazepine receptor-(123)I-iomazenil interactions. (123)I-Iomazenil SPECT and MRI were acquired in 8 healthy volunteers, one of whom had participated in a (11)C-flumazenil PET experiment. The experimental protocol consisted of injections of (123)I-iomazenil and/or unlabeled flumazenil. We developed a kinetic model to integrate the different pharmacokinetics of these 2 ligands. To simplify the model, we assumed linear relationships between iomazenil and flumazenil parameters and adjusted them using a coupled fitting p...Continue Reading

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