Abstract
Purpose
The aim of this study was to investigate the feasibility of assessing dopamine transporter binding after treatment with methylphenidate in the rat using a recently developed high-resolution small animal single-photon emission computed tomograph (TierSPECT) and [123I]FP-CIT.
Methods
[123I]FP-CIT was administered intravenously 1 h after intraperitoneal injection of methylphenidate (10 mg/kg) or vehicle. Animals underwent scanning 2 h after radioligand administration. The striatum was identified by superimposition of [123I]FP-CIT scans with bone metabolism and perfusion scans obtained with 99mTc-DPD and 99mTc-tetrofosmin, respectively. As these tracers do not pass the blood–brain barrier, their distribution permits the identification of extracerebral anatomical landmarks such as the orbitae and the harderian glands. The cerebellum was identified by superimposing [123I]FP-CIT scans with images of brain perfusion obtained with 99mTc-HMPAO.
Results
Methylphenidate-treated animals and vehicle-treated animals yielded striatal equilibrium ratios (V″3) of 0.24±0.26 (mean ± SD) and 1.09±0.42, respectively (t test, two-tailed, p<0.0001). Cortical V″3 values amounted to 0.05±0.28 (methylphenidate) and 0.3±0.39 (saline, p=0.176). This first in vivo study of rat dopamine transporter binding after pre-treatment with methylphenidate showed a mean reduction of 78% in striatal [123I]FP-CIT accumulation.
Conclusion
The results can be interpreted in terms of a pharmacological blockade in the rat striatum and show that in vivo quantitation of dopamine transporter binding is feasible with [123I]FP-CIT and the TierSPECT. This may be of future relevance for in vivo investigations on rat models of attention deficit/hyperactivity disorder. Furthermore, our findings suggest that investigations in other animal models, e.g. of Parkinson’s and Huntington’s disease, may be feasible using SPECT radioligands and small animal imaging systems.
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Acknowledgements
This work was supported by Medice GmbH, Iserlohn, Germany. We also thank Dr. Annemarie Treiber, Dr. Petra Hofmann and Dr. Evalotta Sehrig-Lovén from the TVA, Heinrich-Heine University, Düsseldorf, Germany for their advice and technical assistance.
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Nikolaus, S., Wirrwar, A., Antke, C. et al. Quantitation of dopamine transporter blockade by methylphenidate: first in vivo investigation using [123I]FP-CIT and a dedicated small animal SPECT. Eur J Nucl Med Mol Imaging 32, 308–313 (2005). https://doi.org/10.1007/s00259-004-1615-9
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DOI: https://doi.org/10.1007/s00259-004-1615-9