Pharmacokinetic Analysis of Benzodiazepine Receptor Binding of [123I]Iomazenil in Human Brain

AbstractPurpose. The purpose of this study is to evaluate the central benzodiazepine (BZP) receptor binding of iomazenil (IMZ) by pharmacokinetic analysis and to establish a methodology for the diagnosis of CNS disorders with abnormalities in BZP receptor binding. Methods. BZP receptor binding of IMZ was analyzed kinetically using plasma concentration-time profiles and dynamic single photon emission computed tomography (SPECT) data obtained after the intravenous administration of IMZ to patients with neuropsychiatric diseases. The analysis was based on a 3-compartmental model including the processes of both blood-brain barrier (BBB) transport and BZP receptor binding. Results. Hydrolized metabolite of IMZ was detected in plasma, indicating the need for separation by HPLC. The BBB influx clearance and the receptor binding potential of IMZ in the medial temporal region was reduced in the epileptic patient. Conclusions. Our findings suggest the possibility of detecting the epileptic focus by using our method.

[1]  L. Pieri,et al.  In vitro and in vivo evaluation of iodine-123-Ro 16-0154: a new imaging agent for SPECT investigations of benzodiazepine receptors. , 1990, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[2]  D E Kuhl,et al.  In vivo cerebral metabolism and central benzodiazepine‐receptor binding in temporal lobe epilepsy , 1993, Neurology.

[3]  J. Seibyl,et al.  SPECT measurement of benzodiazepine receptors in human brain with iodine-123-iomazenil: kinetic and equilibrium paradigms. , 1994, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[4]  J. Seibyl,et al.  Human biodistribution and dosimetry of the SPECT benzodiazepine receptor radioligand iodine-123-iomazenil. , 1994, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[5]  Robert B. Innis,et al.  SPECT Quantification of [123I]Iomazenil Binding to Benzodiazepine Receptors in Nonhuman Primates: I. Kinetic Modeling of Single Bolus Experiments , 1994, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[6]  Robert B. Innis,et al.  SPECT Quantification of [123I]Iomazenil Binding to Benzodiazepine Receptors in Nonhuman Primates: II. Equilibrium Analysis of Constant Infusion Experiments and Correlation with in vitro Parameters , 1994, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[7]  Y. Yonekura,et al.  Simple quantification of benzodiazepine receptor binding and ligand transport using iodine-123-iomazenil and two SPECT scans. , 1995, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.