Kinetic modeling of benzodiazepine receptor binding with PET and high specific activity [11C]iomazenil in healthy human subjects

J. Douglas Bremner, Andrew Horti, Lawrence H. Staib, Yolanda Zea-Ponce, Robert Soufer, Dennis S. Charney, Ronald Baldwin

Research output: Contribution to journalArticle

Abstract

Quantitation of the PET benzodiazepine receptor antagonist, [11C]Iomazenil, using low specific activity radioligand was recently described. The purpose of this study was to quantitate benzodiazepine receptor binding in human subjects using PET and high specific activity [11C]Iomazenil. Six healthy human subjects underwent PET imaging following a bolus injection of high specific activity (> 100 Ci/mmol) [11C]iomazenil. Arterial samples were collected at multiple time points after injection for measurement of unmetabolized total and nonprotein-bound parent compound in plasma. Time activity curves of radioligand concentration in brain and plasma were analyzed using two and three compartment model. Kinetic rate constants of transfer of radioligand between plasma, nonspecifically bound brain tissue, and specifically bound brain tissue compartments were fitted to the model. Values for fitted kinetic rate constants were used in the calculation of measures of benzodiazepine receptor binding, including binding potential (the ratio of receptor density to affinity), and product of BP and the fraction of free nonprotein-bound parent compound (V3'). Use of the three compartment model improved the goodness of fit in comparison to the two compartment model. Values for kinetic rate constants and measures of benzodiazepine receptor binding, including BP and V3', were similar to results obtained with the SPECT radioligand [123I]iomazenil, and a prior report with low specific activity [11C]Iomazenil. Kinetic modeling using the three compartment model with PET and high specific activity [11C]Iomazenil provides a reliable measure of benzodiazepine receptor binding.

Original languageEnglish (US)
Pages (from-to)68-77
Number of pages10
JournalSynapse
Volume35
Issue number1
DOIs
StatePublished - 2000
Externally publishedYes

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GABA-A Receptors
Healthy Volunteers
Brain
Injections
Single-Photon Emission-Computed Tomography
iomazenil

Keywords

  • Benzodiazepines
  • Iomazenil
  • Modeling
  • Neuroimaging
  • PET

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology
  • Pharmacology

Cite this

Kinetic modeling of benzodiazepine receptor binding with PET and high specific activity [11C]iomazenil in healthy human subjects. / Bremner, J. Douglas; Horti, Andrew; Staib, Lawrence H.; Zea-Ponce, Yolanda; Soufer, Robert; Charney, Dennis S.; Baldwin, Ronald.

In: Synapse, Vol. 35, No. 1, 2000, p. 68-77.

Research output: Contribution to journalArticle

Bremner, J. Douglas ; Horti, Andrew ; Staib, Lawrence H. ; Zea-Ponce, Yolanda ; Soufer, Robert ; Charney, Dennis S. ; Baldwin, Ronald. / Kinetic modeling of benzodiazepine receptor binding with PET and high specific activity [11C]iomazenil in healthy human subjects. In: Synapse. 2000 ; Vol. 35, No. 1. pp. 68-77.
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