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. 2005 Mar;32(3):308-13. doi: 10.1007/s00259-004-1615-9. Epub 2004 Oct 12.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cerebral Cortex / diagnostic imaging*
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism*
  • Corpus Striatum / diagnostic imaging*
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism*
  • Dopamine Plasma Membrane Transport Proteins
  • Equipment Design
  • Equipment Failure Analysis
  • Feasibility Studies
  • Image Interpretation, Computer-Assisted / methods
  • Iodine Radioisotopes / pharmacokinetics
  • Male
  • Membrane Glycoproteins / antagonists & inhibitors
  • Membrane Glycoproteins / metabolism*
  • Membrane Transport Modulators
  • Membrane Transport Proteins / antagonists & inhibitors
  • Membrane Transport Proteins / metabolism*
  • Methylphenidate / administration & dosage*
  • Nerve Tissue Proteins / antagonists & inhibitors
  • Nerve Tissue Proteins / metabolism*
  • Radiopharmaceuticals / pharmacokinetics
  • Rats
  • Rats, Wistar
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Tissue Distribution / drug effects
  • Tomography, Emission-Computed, Single-Photon / instrumentation
  • Tomography, Emission-Computed, Single-Photon / methods
  • Tomography, Emission-Computed, Single-Photon / veterinary
  • Tropanes / pharmacokinetics*


  • Dopamine Plasma Membrane Transport Proteins
  • Iodine Radioisotopes
  • Membrane Glycoproteins
  • Membrane Transport Modulators
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Radiopharmaceuticals
  • Tropanes
  • 2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane
  • Methylphenidate