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Pretreatment with Haloperidol Reduces ¹²³I-FP-CIT Binding to the Dopamine Transporter in the Rat Striatum: An In Vivo Imaging Study with a Dedicated Small-Animal SPECT Camera

Clinic of Nuclear Medicine, University Hospital Düsseldorf, Düsseldorf, Germany

Correspondence: For correspondence or reprints contact: Susanne Nikolaus, University Hospital Düsseldorf, Moorenstrasse 5, Düsseldorf, Germany D-40225. E-mail: Susanne.Nikolaus{at}uni-duesseldorf.de

Synaptic dopamine is mainly regulated by presynaptic dopamine transporter (DAT) activity. We hypothesized that variations in synaptic dopamine are reflected by variations of DAT radioligand binding. The effect of haloperidol, which increases synaptic dopamine concentrations, was therefore assessed in the rat striatum using ¹²³I-N--fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)-nortropane (¹²³I-FP-CIT) as a DAT radioligand. Methods: Striatal ¹²³I-FP-CIT binding was measured in 24 rats under baseline conditions (no pretreatment) and at 1 h after injection of haloperidol or a vehicle (1 mg/kg) using a small-animal SPECT camera. Results: Baseline equilibrium ratios (V₃'') were 1.32 ± 0.24 (mean ± SD). After the haloperidol injection, V₃'' decreased to 0.99 ± 0.38 (P_2-tailed < 0.0001), corresponding to a mean reduction of DAT binding by 25%. Conclusion: Our results are indicative of competition between the DAT ligand ¹²³I-FP-CIT and synaptic dopamine elevated by haloperidol, suggesting that the assessment of ¹²³I-FP-CIT binding may be suitable to study variations in synaptic dopamine in vivo.

Key Words: FP-CIT • haloperidol • dopamine transporter • molecular imaging • small-animal SPECT

COPYRIGHT © 2009 by the Society of Nuclear Medicine, Inc.

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JNM 2009 50: 11A-12A. [Full Text]