title: Quantitation of benzodiazepine receptor binding with PET [11C]iomazenil and SPECT [123I]iomazenil: preliminary results of a direct comparison in healthy human subjects.
abstract: Although positron emission tomography (PET) and single photon emission computed tomography (SPECT) are increasingly used for quantitation of neuroreceptor binding, almost no studies to date have involved a direct comparison of the two. One study found a high level of agreement between the two techniques, although there was a systematic 30% increase in measures of benzodiazepine receptor binding in SPECT compared with PET. The purpose of the current study was to directly compare quantitation of benzodiazepine receptor binding in the same human subjects using PET and SPECT with high specific activity [11C]iomazenil and [123I]iomazenil, respectively. All subjects were administered a single bolus of high specific activity iomazenil labeled with 11C or 123I followed by dynamic PET or SPECT imaging of the brain. Arterial blood samples were obtained for measurement of metabolite-corrected radioligand in plasma. Compartmental modeling was used to fit values for kinetic rate constants of transfer of radioligand between plasma and brain compartments. These values were used for calculation of binding potential (BP = Bmax/Kd) and product of BP and the fraction of free non-protein-bound parent compound (V3'). Mean values for V3' in PET and SPECT were as follows: temporal cortex 23+/-5 and 22+/-3 ml/g, frontal cortex23+/-6 and 22+/-3 ml/g, occipital cortex 28+/-3 and 31+/-5 ml/g, and striatum 4+/-4 and 7+/-4 ml/g. These preliminary findings indicate that PET and SPECT provide comparable results in quantitation of neuroreceptor binding in the human brain.
authors.affiliation: Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, CT 06520, USA. j.bremner@yale.edu
authors.forename: J D
authors.initials: JD
authors.lastname: Bremner
authors.forename: R
authors.initials: R
authors.lastname: Baldwin
authors.forename: A
authors.initials: A
authors.lastname: Horti
authors.forename: L H
authors.initials: LH
authors.lastname: Staib
authors.forename: C K
authors.initials: CK
authors.lastname: Ng
authors.forename: P Z
authors.initials: PZ
authors.lastname: Tan
authors.forename: Y
authors.initials: Y
authors.lastname: Zea-Ponce
authors.forename: S
authors.initials: S
authors.lastname: Zoghbi
authors.forename: J P
authors.initials: JP
authors.lastname: Seibyl
authors.forename: R
authors.initials: R
authors.lastname: Soufer
authors.forename: D S
authors.initials: DS
authors.lastname: Charney
authors.forename: R B
authors.initials: RB
authors.lastname: Innis
mesh_terms: D000328:Adult; D001667:Binding, Competitive; D001681:Biological Assay; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005442:Flumazenil / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006304:Health Status; D006801:Humans; D008297:Male; D011869:Radioligand Assay; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D011963:Receptors, GABA-A / Q000378:metabolism*; D013997:Time Factors; D014055:Tomography, Emission-Computed; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D019275:Radiopharmaceuticals; D011963:Receptors, GABA-A; D005442:Flumazenil; C063038:iomazenil