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.
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.
Authors: J B Habraken; K de Bruin; M Shehata; J Booij; R Bennink; B L van Eck Smit; E Busemann Sokole Journal: J Nucl Med Date: 2001-12 Impact factor: 10.057
Authors: Christoph Scherfler; Eveline Donnemiller; Michael Schocke; Katja Dierkes; Clemens Decristoforo; Michael Oberladstätter; Christian Kolbitsch; Fritz Zschiegner; Georg Riccabona; Werner Poewe; Gregor Wenning Journal: Neuroimage Date: 2002-09 Impact factor: 6.556
Authors: S P Hume; A A Lammertsma; R Myers; S Rajeswaran; P M Bloomfield; S Ashworth; R A Fricker; E M Torres; I Watson; T Jones Journal: J Neurosci Methods Date: 1996-08 Impact factor: 2.390
Authors: Y Kuge; K Minematsu; Y Hasegawa; T Yamaguchi; H Mori; H Matsuura; N Hashimoto; Y Miyake Journal: J Cereb Blood Flow Metab Date: 1997-01 Impact factor: 6.200
Authors: M Laruelle; C van Dyck; A Abi-Dargham; Y Zea-Ponce; S S Zoghbi; D S Charney; R M Baldwin; P B Hoffer; H F Kung; R B Innis Journal: J Nucl Med Date: 1994-05 Impact factor: 10.057
Authors: Swen Hesse; Karl Strecker; Dirk Winkler; Julia Luthardt; Christoph Scherfler; Annegret Reupert; Christian Oehlwein; Henryk Barthel; Jens-Peter Schneider; Florian Wegner; Philipp Meyer; Jürgen Meixensberger; Osama Sabri; Johannes Schwarz Journal: J Neurol Date: 2008-05-02 Impact factor: 4.849
Authors: Susanne Nikolaus; Christina Antke; Markus Beu; Konstantin Kley; Andreas Wirrwar; Joseph P Huston; Hans-Wilhelm Müller Journal: Eur J Nucl Med Mol Imaging Date: 2010-11-26 Impact factor: 9.236