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European Journal of Nuclear Medicine and Molecular Imaging
Published in: European Journal of Nuclear Medicine and Molecular Imaging 3/2005

01-03-2005 | Original Article

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

Authors: Susanne Nikolaus, Andreas Wirrwar, Christina Antke, Shahram Arkian, Nils Schramm, Hans-Wilhelm Müller, Rolf Larisch

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 3/2005

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Abstract

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.
Literature
1.
Dougherty DD, Bonab AA, Spencer TJ, Rauch SL, Madras BK, Fischman AJ. Dopamine transporter density in patients with attention deficit hyperactivity disorder. Lancet 1999;354:2132–3.CrossRefPubMed
2.
Dresel S, Krause J, Krause KH, LaFougere C, Brinkbaumer K, Kung HF, et al. Attention deficit hyperactivity disorder: binding of [99mTc]TRODAT-1 to the dopamine transporter before and after methylphenidate treatment. Eur J Nucl Med 2000;27:1518–24. DOI 10.1007/s002590000330.CrossRefPubMed
3.
Volkow ND, Fowler JS, Wang G, Ding Y, Gatley SJ. Mechanism of action of methylphenidate: insights from PET imaging studies. J Atten Disord 2002;6(Suppl 1):S31–43.PubMed
4.
Krause KH, Dresel SH, Krause J, Kung HF, Tatsch K. Increased striatal dopamine transporter in adult patients with attention deficit hyperactivity disorder: effects of methylphenidate as measured by single photon emission computed tomography. Neurosci Lett 2002;285:107–10.CrossRefPubMed
5.
Volkow ND, Wang GJ, Fowler JS, Gatley SJ, Logan J, Ding YS, et al. Dopamine transporter occupancies in the human brain induced by therapeutic doses of oral methylphenidate. Am J Psychiatry 1998;155:1325–31.PubMed
6.
Dresel SH, Kung MP, Plossl K, Meegalla SK, Kung HF. Pharmacological effects of dopaminergic drugs on in vivo binding of [99mTc]TRODAT-1 to the central dopamine transporters in rats. Eur J Nucl Med 1998;25:31–93. DOI 10.1007/s002590050191.CrossRefPubMed
7.
Reneman L, De Bruin K, Lavalaye J, Gunning WB, Booij J. Addition of a 5-HT receptor agonist to methylphenidate potentiates the reduction of [123I]FP-CIT binding to dopamine transporters in rat frontal cortex and hippocampus. Synapse 2001;39:193–200. DOI 10.1002/1098-2396(20010301)39:3<193∷AID-SYN1000>3.0.CO;2-F.CrossRefPubMed
8.
Wirrwar A, Schramm N, Vosberg H, Muller-Gartner H-W. High resolution SPECT in small animal research. Rev Neurosci 2001;12:187–93.
9.
Nikolaus S, Wirrwar A, Klimke A, Beu M, Forutan F, Vosberg H, et al. State-of-the-art in high-resolution imaging of small animals with PET and SPECT. In: Mohan RM, editor. Research advances in nuclear medicine. Kerala: Global Research Networks; 2002. p. 13–29.
10.
Acton PD, Choi SR, Plossl K, Kung HF. Quantification of dopamine transporters in the mouse brain using ultra-high resolution single-photon emission tomography. Eur J Nucl Med Mol Imaging 2002;29:691–8. DOI 10.1007/s00259-002-0776-7.CrossRefPubMed
11.
Scherfler C, Donnemiller E, Schocke M, Dierkes K, Decristoforo C, Oberladstatter M, et al. Evaluation of striatal dopamine transporter function in rats by in vivo beta-[123I]CIT pinhole SPECT. Neuroimage 2002;17:128–41.CrossRefPubMed
12.
Booij J, de Bruin K, Habraken JB, Voorn P. Imaging of dopamine transporters in rats using high-resolution pinhole single-photon emission tomography. Eur J Nucl Med Mol Imaging 2002;29:1221–4. DOI 10.1007/s00259-002-0845-y.CrossRefPubMed
13.
Schramm N, Wirrwar A, Sonnenberg F, Halling H. Compact high resolution detector for small animal SPECT. IEEE Trans Nucl Sci 2000;47:1163–7.CrossRef
14.
Seibyl JP, Marek K, Sheff K, Zoghbi S, Baldwin RM, Charney DS, et al. Iodine-123-beta-CIT and iodine-123-FPCIT SPECT measurement of dopamine transporters in healthy subjects and Parkinson’s patients. J Nucl Med 1998;39:1500–8.PubMed
15.
Booij J, Hemelaar JTGM, Speelman JD, de Bruin K, Janssen AGM, van Royen EA. One-day protocol for imaging of the nigrostriatal pathway in Parkinson’s disease by [123I]FP-CIT. J Nucl Med 1999;40:753–61.PubMed
16.
Laruelle M, van Dyck C, Abi-Dargham A, Zea-Ponce Y, Zoghbi SS, Charney DS, et al. Compartmental modeling of iodine-123-iodobenzofuran binding to dopamine D2 receptors in healthy subjects. J Nucl Med 1994;35:743–54.PubMed
17.
Ichise M, Meyer JH, Yonekura Y. An introduction to PET and SPECT neuroreceptor quantification models. J Nucl Med 2001;42:755–63.PubMed
18.
Habraken JB, de Bruin K, Shehata M, Booij J, Bennink R, van Eck Smit BL, Busemann Sokole E. Evaluation of high-resolution pinhole SPECT using a small rotating animal. J Nucl Med 2001;42:1863–9.PubMed
19.
Hume SP, Lammertsma AA, Myers R, Rajeswaran S, Bloomfield PM, Ashworth S, et al. The potential of high-resolution positron emission tomography to monitor striatal dopaminergic function in rat models of disease. J Neurosci Methods 1996;67:103–12.CrossRefPubMed
20.
Nikolaus S, Larisch R, Beu M, Vosberg H, Muller-Gartner H-W. Imaging of striatal dopamine D2 receptors with a PET system for small laboratory animals in comparison with storage phosphor autoradiography: a validation study with 18F-(N-methyl)benperidol. J Nucl Med 2001;42:1691–6.PubMed
21.
Nikolaus S, Larisch R, Beu M, Hamacher K, Forutan F, Vosberg H, Muller H-W. In vivo measurement of D2 receptor density and affinity for 18F-(3-N-methyl)benperidol in the rat striatum with a PET system for small laboratory animals. J Nucl Med 2003;44:618–24.PubMed
22.
Kuge Y, Minematsu K, Hasegawa Y, Yamaguchi T, Mori H, Matsuura H, et al. Positron emission tomography for quantitative determination of glucose metabolism in normal and ischemic brains in rats: an insoluble problem by the Harderian glands. J Cereb Blood Flow Metab 1997;17:116–20.CrossRefPubMed
Metadata
Title
Quantitation of dopamine transporter blockade by methylphenidate: first in vivo investigation using [123I]FP-CIT and a dedicated small animal SPECT
Authors
Susanne Nikolaus
Andreas Wirrwar
Christina Antke
Shahram Arkian
Nils Schramm
Hans-Wilhelm Müller
Rolf Larisch
Publication date
01-03-2005
Publisher
Springer-Verlag
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 3/2005
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-004-1615-9

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