Quantitation of dopamine transporter blockade by methylphenidate: first in vivo investigation using [123I]FP-CIT and a dedicated small animal SPECT

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 (V₃) of 0.24±0.26 (mean ± SD) and 1.09±0.42, respectively (t test, two-tailed, p<0.0001). Cortical V₃ 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 Parkinsons and Huntingtons disease, may be feasible using SPECT radioligands and small animal imaging systems.