Document Detail


Kinetic modelling and occupancy measures of the norepinephrine transporters in baboons using SPECT with (123) I-INER.
MedLine Citation:
PMID:  23042643     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
This study aims to investigate the pharmacokinetics of a recently developed radiotracer for imaging of the norepinephrine transporter (NET) in baboon brain, (123) I-INER, using single photon emission computed tomography (SPECT). In addition, it also aims to determine NET occupancy by atomoxetine and reboxetine, two selective norepinephrine reuptake inhibitors, using (123) I-INER in baboons. Baseline and pre-blocking studies with a high dose of atomoxetine (0.85 mg/kg) were conducted in three baboons using SPECT with (123) I-INER administered as a bolus. Kinetic modelling analysis was investigated for different models, namely invasive and reference tissue models. Bolus plus constant infusion experiments with displacement at equilibrium using six different doses of atomoxetine (0.03-0.85 mg/kg) and four different doses of reboxetine (0.5-3.0 mg/kg) were carried out in several baboons to obtain occupancy measurements as a function of dose for the two NET selective drugs. Results showed that reference tissue models can be used to estimate binding potential values and occupancy measures of (123) I-INER in different brain regions. In addition the apparent volume of distribution was estimated by dividing concentration in tissue by the concentration in blood at 3 hours post-injection. After administration of atomoxetine or reboxetine, a dose-dependent occupancy was observed in brain regions known to contain high densities of NET. In conclusion, pharmacokinetic properties of (123) I-INER were successfully described and obtained results may be used to simplify future data acquisition and image processing. Dose-dependent NET occupancy for two selective norepinephrine reuptake inhibitors was successfully measured in vivo in baboon brain using SPECT and (123) I-INER. Synapse, 2012. © 2012 Wiley Periodicals, Inc.
Authors:
Adriana Alexandre S Tavares; Olivier Barret; Jeffery Batis; David Alagille; Andrei Koren; Caroline Papin; Greg Kudej; Katie Nice; Jeffrey H Kordower; Kelly P Cosgrove; Tracy Kloczynski; Eric Brenner; John Seibyl; Gilles Tamagnan
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-8
Journal Detail:
Title:  Synapse (New York, N.Y.)     Volume:  -     ISSN:  1098-2396     ISO Abbreviation:  Synapse     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8806914     Medline TA:  Synapse     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 Wiley Periodicals, Inc.
Affiliation:
Institute of Neuroscience and Psychology, College of Medical, Veterinary and Life Sciences, University of Glasgow, UK. atavares@mnimaging.com.
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