期刊
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
卷 32, 期 3, 页码 308-313出版社
SPRINGER
DOI: 10.1007/s00259-004-1615-9
关键词
methylphenidate; [I-123]FP-CIT; dopamine transporter; small animal tomography; attention deficit/hyperactivity disorder
Purpoe: 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 [I-123]FP-CIT. Methods: [I-123]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 [I-123]FP-CIT scans with bone metabolism and perfusion scans obtained with Tc-99m-DPD and Tc-99m-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 [I-123]FP-CIT scans with images of brain perfusion obtained with Tc-99m-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 [I-123]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 [I-123]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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