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[123I]Iodobenzamide binding to the rat dopamine D2 receptor in competition with haloperidol and endogenous dopamine—an in vivo imaging study with a dedicated small animal SPECT

  • Susanne NikolausEmail author
  • Rolf Larisch
  • Andreas Wirrwar
  • Marlyse Jamdjeu-Nouné
  • Christina Antke
  • Markus Beu
  • Nils Schramm
  • Hans-Wilhelm Müller
Original Article

Abstract

Purpose

This study assessed [123I]iodobenzamide binding to the rat dopamine D2 receptor in competition with haloperidol and endogenous dopamine using a high-resolution small animal SPECT.

Methods

Subsequent to baseline quantifications of D2 receptor binding, imaging studies were performed on the same animals after pre-treatment with haloperidol and methylphenidate, which block D2 receptors and dopamine transporters, respectively.

Results

Striatal baseline equilibrium ratios (V 3″) of [123I]iodobenzamide binding were 1.42±0.31 (mean±SD). After pre-treatment with haloperidol and methylphenidate, V 3″ values decreased to 0.54±0.46 (p<0.0001) and 0.98±0.48 (p=0.009), respectively.

Conclusion

The decrease in [123I]iodobenzamide binding induced by pre-treatment with haloperidol reflects D2 receptor blockade, whereas the decrease in receptor binding induced by pre-treatment with methylphenidate can be interpreted in terms of competition between [123I]IBZM and endogenous dopamine. Findings show that multiple in vivo measurements of [123I]iodobenzamide binding to D2 receptors in competition with exogenous and endogenous ligands are feasible in the same animal. This may be of future relevance for the in vivo evaluation of novel radioligands as well as for studying the interrelations between pre- and/or postsynaptic radioligand binding and different levels of endogenous dopamine.

Keywords

[123I]IBZM Haloperidol Methylphenidate Small animal tomography 

Notes

Acknowledgements

This work was supported by Medice GmbH, Iserlohn, Germany.

References

  1. 1.
    Schramm N, Wirrwar A, Sonnenberg F, Halling H. Compact high resolution detector for small animal SPECT. IEEE Trans Nucl Sci 2000;47:1163–7CrossRefGoogle Scholar
  2. 2.
    Nikolaus S, Wirrwar A, Antke C, et al. 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 2004; Published online Oct. 12, DOI:  10.1007/s00259-004-1615-9
  3. 3.
    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;29:691–8PubMedCrossRefGoogle Scholar
  4. 4.
    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;17:128–1PubMedCrossRefGoogle Scholar
  5. 5.
    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;29:1221–4PubMedCrossRefGoogle Scholar
  6. 6.
    Acton PD, Hou C, Kung MP, Plossl K, Keeney CL, Kung HF. Occupancy of dopamine D2 receptors in the mouse brain measured using ultra-high-resolution single-photon emission tomography and [123]IBF. Eur J Nucl Med Mol Imaging 2002;29:1507–15PubMedCrossRefGoogle Scholar
  7. 7.
    Kung HF, Guo YZ, Billings J, Xu X, Mach RH, Blau M, et al. Preparation and biodistribution of [125I]IBZM: a potential CNS D-2 dopamine receptor imaging agent. Int J Rad Appl Instrum B 1988;15:195–201CrossRefGoogle Scholar
  8. 8.
    Nyberg S, Nilsson U, Okubo Y, Halldin C, Farde L. Implications of brain imaging for the management of schizophrenia. Int Clin Psychopharmacol 1998;13 Suppl 3:15–20CrossRefGoogle Scholar
  9. 9.
    Laruelle M. Imaging synaptic neurotransmission with in vivo binding competition techniques: a critical review. J Cereb Blood Flow Metab 2000;20:423–51PubMedCrossRefGoogle Scholar
  10. 10.
    Innis RB, Malison RT, al-Tikriti M, Hoffer PB, Sybirska EH, Seibyl JP, et al. Amphetamine-stimulated dopamine release competes in vivo for [123I]IBZM binding to the D2 receptor in nonhuman primates. Synapse 1992;10:177–84PubMedCrossRefGoogle Scholar
  11. 11.
    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:S31–43PubMedGoogle Scholar
  12. 12.
    Booij J, Korn P, Linszen DH, van Royen EA. Assessment of endogenous dopamine release by methylphenidate challenge using iodine-123 iodobenzamide single-photon emission tomography. Eur J Nucl Med 1997;24:674–7PubMedGoogle Scholar
  13. 13.
    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;35:743–54PubMedGoogle Scholar
  14. 14.
    Hume SP, Gunn RN, Jones T. Pharmacological constraints associated with positron emission tomographic scanning of small laboratory animals. Eur J Nucl Med 1998;25:173–6PubMedCrossRefGoogle Scholar
  15. 15.
    Seibyl JP, Woods SW, Zoghbi SS, Baldwin RM, Dey HM, Goddard AW, et al. Dynamic SPECT imaging of dopamine D2 receptors in human subjects with iodine-123-IBZM. J Nucl Med 1992;33:1964–71PubMedGoogle Scholar
  16. 16.
    Nikolaus S, Wirrwar A, Larisch R, Schramm N, Antke C, Müller HW, A landmark-based approach for the quantitation of receptor and transporter binding in the rat using small animal SPECT and PET. IEEE NSS/MIC/SNPS RTSD Conf Rec 2004.Google Scholar
  17. 17.
    Ichise M, Meyer JH, Yonekura Y. An introduction to PET and SPECT neuroreceptor quantification models. J Nucl Med 2001;42:755–63PubMedGoogle Scholar
  18. 18.
    Seeman P, Grigoriadis D. Dopamine receptors in brain and periphery. Neurochem Int 1987;10:1–25PubMedCrossRefGoogle Scholar
  19. 19.
    Verhoeff NP, Bobeldijk M, Feenstra MG, Boer GJ, Maas MA, Erdtsieck-Ernste E, et al. In vitro and in vivo D2-dopamine receptor binding with [123I]S(−) iodobenzamide ([123I]IBZM) in rat and human brain. Int J Rad Appl Instrum B 1991;18:837–46PubMedCrossRefGoogle Scholar
  20. 20.
    de Paulis T, Janowsky A, Kessler RM, Clanton JA, Smith HE. (S)-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-[125I]iodo-2-methoxybenzamide hydrochloride, a new selective radioligand for dopamine D-2 receptors. J Med Chem 1988;31:2027–33PubMedCrossRefGoogle Scholar
  21. 21.
    Pehek EA. Comparison of effects of haloperidol administration on amphetamine-stimulated dopamine release in the rat medial prefrontal cortex and dorsal striatum. J Pharmacol Exp Ther 1999;289:14–23PubMedGoogle Scholar
  22. 22.
    Ishizu K, Smith DF, Bender D, Danielsen E, Hansen SB, Wong DF, et al. Positron emission tomography of radioligand binding in porcine striatum in vivo: haloperidol inhibition linked to endogenous ligand release. Synapse 2000;38:87–101PubMedCrossRefGoogle Scholar
  23. 23.
    Freeman KA, Tallarida RJ. A quantitative study of dopamine control in the rat striatum. J Pharmacol Exp Ther 1994;268:629–38PubMedGoogle Scholar
  24. 24.
    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;67:103–12PubMedGoogle Scholar
  25. 25.
    Nikolaus S, Larisch R, Beu M, Vosberg H, Müller-Gartner HW. 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;42:1691–6PubMedGoogle Scholar
  26. 26.
    Nikolaus S, Larisch R, Beu M, Hamacher K, Forutan F, Vosberg H, et al. 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;44:618–24PubMedGoogle Scholar
  27. 27.
    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;17:116–20PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Susanne Nikolaus
    • 1
    Email author
  • Rolf Larisch
    • 1
  • Andreas Wirrwar
    • 1
  • Marlyse Jamdjeu-Nouné
    • 1
  • Christina Antke
    • 1
  • Markus Beu
    • 1
  • Nils Schramm
    • 2
  • Hans-Wilhelm Müller
    • 1
  1. 1.Clinic of Nuclear MedicineHeinrich-Heine UniversityDüsseldorfGermany
  2. 2.Central Laboratory for ElectronicsResearch Center JülichJülichGermany

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