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Search for PET probes for imaging the globus pallidus studied with rat brainex vivo autoradiography

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Abstract

We have evaluated the feasibility of using four positron emission tomography (PET) tracers for imaging the globus pallidus byex vivo autoradiography in rats. The tracers investigated were [11C]KF18446, [11C]SCH 23390 and [11C]raclopride for mapping adenosine A2A, dopamine D1 and dopamine D2 receptors, respectively, and [18F]FDG. The highest uptake by the globus pallidus was found for [11C]SCH 23390, followed by [18F]FDG, [11C]KF18446 and [11C]raclopride. The receptor-specific uptake by the globus pallidus was observed in [11C]KF18446 and [11C]SCH 23390, but not in [11C]raclopride. Uptake ratios of globus pallidus to the striatum for [18F]FDG and [11C]KF18446 were approximately 0.6, which was twice as large as that for [11C]SCH 23390. In a rat model of degeneration of striatopallidal γ-aminobutyric acid-ergic-enkephalin neurons induced by intrastriatal injection of quinolinic acid, the uptake of [11C]KF18446 by the striatum and globus pallidus was remarkably reduced. To prove the visualization of the globus pallidus by PET with [18F]FDG and [11C]KF18446, PET-MRI registration technique and advances in PET technologies providing high-resolution PET scanner will be required. The metabolic activity of the globus pallidus could then be measured by PET with [18]FDG and [11C]KF18446 may be a candidate tracer for imaging the pallidal terminals projecting from the striatum.

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References

  1. Wagner HN Jr, Burns HD, Dannals RF, Wong DF, Langstrom B, Duelfer T, et al. Imaging dopamine receptors in the human brain by positron emission tomography.Science 221: 1264–1266, 1983.

    Article  CAS  PubMed  Google Scholar 

  2. Mazière, B, Mazière M. Where have we got to with neuroreceptor mapping of the human brain?Eur J Nucl Med 16: 817–835, 1990.

    Article  PubMed  Google Scholar 

  3. Sawle GV, Brooks DJ. Positron emission tomography studies of neurotransmitter systems.J Neurol 237: 451–456, 1990.

    Article  CAS  PubMed  Google Scholar 

  4. Booij J, Tissingh G, Winogrodzka A, van Royen EA. Imaging of the dopaminergic neurotransmission system using single-photon emission tomography and positron emission tomography in patients with parkinsonism.Eur J Nucl Med 26: 171–181, 1999.

    Article  CAS  PubMed  Google Scholar 

  5. Mazière B, Coenen HH, Halldin C, Någren K, Pike VW. PET radioligands for dopamine receptors and re-uptake sites: chemistry and biochemistry.Nucl Med Biol 19: 497–512, 1992.

    Google Scholar 

  6. Alexander GE, DeLong MR, Strick PL. Parallel organization of functionally segregated circuits linking basal ganglia and cortex.Ann Rev Neurosci 9: 357–381, 1986.

    Article  CAS  PubMed  Google Scholar 

  7. Alexander GE, Crutcher MD. Functional architecture of basal ganglia circuits: Neural substrates of parallel processing.Trends Neurosci 13: 266–271, 1990.

    Article  CAS  PubMed  Google Scholar 

  8. O'Connor WT. Functional neuroanatomy of the basal ganglia as studied by dual-probe microdialysis.Nucl Med Biol 25: 743–746, 1998.

    Article  PubMed  Google Scholar 

  9. Barone P, Tucci I, Parashos SA, Chase TN. D-1 dopamine receptor changes after striatal quinolinic acid lesion.Eur J Pharmacol 138: 141–145, 1987.

    Article  CAS  PubMed  Google Scholar 

  10. Gerfen CR, Engber TM, Mahan LC, Susel Z, Chase TN, Monsma FJ, et al. D1 and D2 dopamine receptor-regulated gene expression of strionigral and striopallidal neurons.Science 250: 1429–1432, 1990.

    Article  CAS  PubMed  Google Scholar 

  11. Gerfen CR, McGinty JF, Young WS III. Dopamine differentially regulates dynorphin, substance P, and enkephalin expression in striatal neurons:In situ hybridization histochemical analysis.J Neurosci 11: 1016–1031, 1991.

    CAS  PubMed  Google Scholar 

  12. Le Moine C, Normand E, Guitteny AF, Fouque B, Teoule R, Bloch B. Dopamine receptor gene expression by enkephalin neurons in rat forebrain.Proc Natl Acad Sci USA 87: 230–234, 1990.

    Article  PubMed  Google Scholar 

  13. Le Moine C, Normand E, Bloch B. Phenotypical characterization of the rat striatal neurons expressing the D1 dopamine receptor gene.Proc Natl Acad Sci USA 88: 4205–4209, 1991.

    Article  PubMed  Google Scholar 

  14. Lantons PL, Graham DI. eds.Greenfield's Neuropathology. London, Edward Arnold, 1997.

    Google Scholar 

  15. Robertson RG, Farmery SM, Sambrook MA, Crossman AR. Dyskinesia in the primate following injection of an excitatory amino acid antagonist into the medial segment of the globus pallidus.Brain Res 476: 317–322, 1989.

    Article  CAS  PubMed  Google Scholar 

  16. Mink JW, Thach WT. Basal ganglia motor control. III. Pallidal ablation: normal reaction time, muscle cocontraction, and slow movement.J Neurophysiol 65: 330–351, 1991.

    CAS  PubMed  Google Scholar 

  17. Laitinen LV, Bergenheim AT, Hariz MI. Ventroposterolateral pallidotomy can abolish all parkinsonian symptoms.Stereotact Funct Neurosurg 58: 14–21, 1992.

    Article  CAS  PubMed  Google Scholar 

  18. Iacono RP, Lonser RR, Mandybur G, Yamada S. Stimulation of the globus pallidus in Parkinson's disease.Br J Neurosurg 9: 505–510, 1995.

    Article  CAS  PubMed  Google Scholar 

  19. Jarvis MF, Williams M. Direct autoradiographic localization of adenosine A2 receptors in the rat brain using the A2-selective agonist, [3H]CGS 21680.Eur J Pharmacol 168: 243–246, 1989.

    Article  CAS  PubMed  Google Scholar 

  20. Parkinson FE, Fredholm BB. Autoradiographic evidence for G-protein coupled A2-receptors in rat neostriatum using [3H]-CGS21680 as a ligand.Naunyn-Schmied Arch Pharmacol 342: 85–89, 1990.

    Article  CAS  Google Scholar 

  21. Palmer TM, Stiles GL. Adenosine receptors.Neuropharmacology 34: 683–694, 1995.

    Article  CAS  PubMed  Google Scholar 

  22. Fink JS, Weaver DR, Rivkees SA, Peterfreund RA, Pollack AE, Adler EM, Reppert SM. Molecular cloning of the rat A2 adenosine receptor: selective co-expression with D2 dopamine receptors in rat striatum.Mol Brain Res 14: 186–195, 1992.

    Article  CAS  PubMed  Google Scholar 

  23. Augood SJ, Emson PC. Adenosine A2a receptor mRNA is expressed by enkephalin cells but not by somatostatin cells in rat striatum: a co-expression study.Mol Brain Res 22: 204–210, 1994.

    Article  CAS  PubMed  Google Scholar 

  24. Pollack AE, Harrison MB, Wooten GF, Fink JS. Differential localization of A2a adenosine receptor mRNA with D1 and D2 dopamine receptor mRNA in striatal output pathways following a selective lesion of striatonigral neurons.Brain Res 631: 161–166, 1993.

    Article  CAS  PubMed  Google Scholar 

  25. Schiffmann SN, Jacobs O, Vanderhaeghen JJ. Striatal restricted adenosine A2 receptor (RDC8) is expressed by enkephalin but not by substance P neurons: anin situ hybridization histochemistry study.J Neurochem 57: 1062–1067, 1991.

    Article  CAS  PubMed  Google Scholar 

  26. Martinez-Mir MI, Probst A, Palacios JM. Adenosine A2 receptors: selective localization in the human basal ganglia and alterations with disease.Neuroscience 42: 697–706, 1991.

    Article  CAS  PubMed  Google Scholar 

  27. Ishiwata K, Noguchi N, Wakabayashi S, Shimada J, Ogi N, Nariai T, et al. Carbon-11 labeled KF18446: a potential CNS adenosine A2a receptor ligand.J Nucl Med 41: 345–354, 2000.

    CAS  PubMed  Google Scholar 

  28. Ishiwata K, Ogi N, Shimada J, Nonaka H, Tanaka A, Suzuki F, et al. Further characterization of a CNS adenosine A2a receptor ligand [11C]KF18446 within vitro autoradiography andin vivo tissue uptake.Ann Nucl Med 14: 81–89, 2000.

    Article  CAS  PubMed  Google Scholar 

  29. Svenningsson P, Hall H, Sedvall G, Fredholm BB. Distribution of adenosine receptors in the postmortem human brain: an extended autoradiographic study.Synapse 27: 322–335, 1997.

    Article  CAS  PubMed  Google Scholar 

  30. Sokoloff L. The [14C]deoxyglucose method for the quantitative determination of local cerebral glucose utilization: theoretical and practical considerations. InCerebral Metabolism and Neural Function, Passonneau JV, Hawkins RA, Lust WD, Welsh FA (eds.), Baltimore, Williams and Wilkins, pp. 319–330, 1980.

    Google Scholar 

  31. Ishiwata K, Hayakawa N, Ogi N, Oda K, Toyama H, Endo K, et al. Comparison of three PET dopamine D2-like receptor ligands, [11C]raclopride, [11C]nemonapride and [11C]N-methylspiperone, in rats.Ann Nucl Med 13: 161–167, 1999.

    Article  CAS  PubMed  Google Scholar 

  32. Ishiwata K, Ogi N, Tanaka A, Senda M. Quantitativeex vivo andin vitro receptor autoradiography using11C-labeled ligands and an imaging plate: a study with a dopamine D2-like receptor ligand [11C]nemonapride.Nucl Med Biol 26: 291–296, 1999.

    Article  CAS  PubMed  Google Scholar 

  33. Levivier M, Holemans S, Togasaki DM, Maloteaux JM, Brotchi J, Przedborski S. Quantitative assessment of quinolinic acid-induced striatal toxicity in rats using radioligand binding assays.Neurol Res 16: 194–200, 1994.

    CAS  PubMed  Google Scholar 

  34. Hayakawa N, Uemura K, Ishiwata K, Shimada Y, Ogi N, Nagaoka T, et al. A PET-MRI registration technique for PET studies of the rat brain.Nucl Med Biol 27: 121–125, 2000.

    Article  CAS  PubMed  Google Scholar 

  35. Paxinos G, Watson C.The Rat Brain in Stereotaxic Coordinates. 2nd ed., San Diego, Academic Press, Inc., 1986.

    Google Scholar 

  36. Senda M. Mapping cortical functions using PET activation technique. InNew Horizons in Neuropsychology, Sugishita M (ed.), Amsterdam, Elsevier, pp. 23–34, 1994.

    Google Scholar 

  37. Ardekani BA, Braun M, Hutton BF, Kanno I, Iida H. A fully automatic multimodality image registration algorithm.J Comput Assist Tomogr 19: 615–623, 1995.

    Article  CAS  PubMed  Google Scholar 

  38. Coyle JT, Schwarcz R. Lesion of striatal neurons with kainic acid provides a model for Huntington's chorea.Nature 263: 244–246, 1976.

    Article  CAS  PubMed  Google Scholar 

  39. Schwarcz R, Whetsell WO Jr, Mangano RM. Quinolinic acid: an endogenous metabolite that produces axon-sparing lesions in rat brain.Science 219: 316–318, 1982.

    Article  Google Scholar 

  40. Foster AC, Whetsell WO Jr, Bird ED, Schwarcz R. Quinolinic acid phosphoribosyltransferase in human and rat brain: activity in Huntington's disease and in quinolinatelesioned rat striatum.Brain Res 336: 207–214, 1985.

    Article  CAS  PubMed  Google Scholar 

  41. van der Weide J, De Vries JB, Tepper PG, Horn AS. The effects of kainic acid and 6-hydroxydopamine lesions, metal ions and GTP onin vitro binding of the D-2 dopamine agonist, [3H]N-0437, to striatal membranesEur J Pharmacol 143: 101–107, 1989.

    Google Scholar 

  42. Levivier M, Gash DM, Przedborski S. Time course of the neuroprotective effect of transplantation on quinolinic acid-induced lesions of the striatum.Neuroscience 69: 43–50, 1995.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Showa Pharmaceutical University, Showa, Japan

    Nobuo Ogi & Akira Tanaka

  2. Drug Discovery Research Laboratories, Pharmaceutical Research Institute, Kyowa Hakko Kogyo Company, Kyowa, Japan

    Junichi Shimada & Fumio Suzuki

  3. Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, 1-1 Nakacho, 173-0022, Itabashi, Tokyo, Japan

    Kiichi Ishiwata, Nobuo Ogi, Wei-Fang Wang, Kenji Ishii & Michio Senda

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  1. Kiichi Ishiwata
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  2. Nobuo Ogi
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Correspondence to Kiichi Ishiwata.

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Ishiwata, K., Ogi, N., Shimada, J. et al. Search for PET probes for imaging the globus pallidus studied with rat brainex vivo autoradiography. Ann Nucl Med 14, 461–466 (2000). https://doi.org/10.1007/BF02988292

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  • DOI: https://doi.org/10.1007/BF02988292

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