title: Quantitation of dopamine transporter blockade by methylphenidate: first in vivo investigation using [123I]FP-CIT and a dedicated small animal SPECT.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.affiliation: Clinic of Nuclear Medicine, Heinrich-Heine University, 40225, Düsseldorf, Germany. susanne.nikolaus@uni-duesseldorf.de
authors.forename: Susanne
authors.initials: S
authors.lastname: Nikolaus
authors.forename: Andreas
authors.initials: A
authors.lastname: Wirrwar
authors.forename: Christina
authors.initials: C
authors.lastname: Antke
authors.forename: Shahram
authors.initials: S
authors.lastname: Arkian
authors.forename: Nils
authors.initials: N
authors.lastname: Schramm
authors.forename: Hans-Wilhelm
authors.initials: HW
authors.lastname: Müller
authors.forename: Rolf
authors.initials: R
authors.lastname: Larisch
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism*; D003342:Corpus Striatum / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D004867:Equipment Design; D019544:Equipment Failure Analysis; D005240:Feasibility Studies; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D008297:Male; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008774:Methylphenidate / Q000008:administration & dosage*; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution / Q000187:drug effects; D015899:Tomography, Emission-Computed, Single-Photon / Q000295:instrumentation / Q000379:methods / Q000662:veterinary; D014326:Tropanes / Q000493:pharmacokinetics*
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D019275:Radiopharmaceuticals; D014326:Tropanes; C087552:2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane; D008774:Methylphenidate