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- Title
Kinetic modeling and occupancy measures of the norepinephrine transporters in baboons using single photon emission computed tomography with <sup>123</sup>I-INER.
- Authors
Dos Santos Tavares, Adriana Alexandre; Barret, Olivier; Batis, Jeffery; Alagille, David; Koren, Andrei; Papin, Caroline; Kudej, Greg; Nice, Katie; Kordower, Jeffrey H.; Cosgrove, Kelly P.; Kloczynski, Tracy; Brenner, Eric; Seibyl, John; Tamagnan, Gilles
- Abstract
This study aims to investigate the pharmacokinetics of a recently developed radiotracer for imaging of the norepinephrine transporter (NET) in baboon brain, 123I-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 123I-INER in baboons. Baseline and preblocking studies with a high dose of atomoxetine (0.85 mg/kg) were conducted in three baboons using SPECT with 123I-INER administered as a bolus. Kinetic modeling 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 123I-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 postinjection. 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 123I-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 123I-INER. Synapse, 2013. © 2012 Wiley Periodicals, Inc.
- Publication
Synapse, 2013, Vol 67, Issue 1, p30
- ISSN
0887-4476
- Publication type
Article
- DOI
10.1002/syn.21613