Skip to main content
SpringerLink
Log in

PET studies of dopamine receptor distribution using [18F]fluoroethylspiperone: findings in disorders related to the dopaminergic system

  • Full Papers
  • Published:
Journal of Neural Transmission / General Section JNT Aims and scope Submit manuscript

Summary

PET studies of dopamine D2-receptor binding were performed in thirty patients with various disorders related to the dopaminergic system and in six healthy controls. Uptake of [18F]fluoroethylspiperone in caudate over three hours was analyzed in terms of several indices of receptor binding: caudateto-cerebellum activity ratio, concentration of ligand as percentage of injected dose, caudate-to-blood radioactivity ratio, slope of tracer uptake curves, binding potential, kinetic constants of a three compartment model. In 14 patients brain glucose metabolism was also measured. Data on medicated patients demonstrate that the average values of most of the above parameters indicate the decreased number of available D2-receptors whereby, besides an age dependent decline, the caudate-to-cerebellum ratio affords the relatively best distinction among diagnostic groups. In individual cases, large variability among subjects permits only the classification of severe pathologies. Morphological damage and neuronal loss in the striatum may also cause abnormal low values both for the indices of receptor binding and for glucose consumption, thus providing a possible pathogenetic link between receptor dysfunction and impaired energy metabolism.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Baron JC, Mazière B, Loc'h C, Cambon H, Sgouropoulos P, Bonnet AM, Agid Y (1986) Loss of striatal [76Br]bromospiperone binding sites demonstrated by positron emission tomography in progressive supranuclear palsy. J Cereb Blood Flow Metab 6: 131–136

    Google Scholar 

  • Block D, Coenen HH, Laufer P, Stöcklin G (1986) N.c.a.18F-fluoroalkylation via nucleophilic fluorination of disubstituted alkanes and application to the preparation of N-[18F]-fluoroethylspiperone. J Label Comp Radiopharm 23: 1042–1044

    Google Scholar 

  • Bokobza B, Ruberg M, Scatton B, Javoy-Agid F, Agid Y (1984) [3H]spiperone binding, dopamine and HVA concentrations in Parkinson's disease and supranuclear palsy. Eur J Pharmacol 99: 167–175

    Google Scholar 

  • Chugani DC, Ackermann RF, Phelps ME (1988) In vivo [3H]spiperone binding: evidence for accumulation in corpus striatum by agonist-mediated receptor internalization. J Cereb Blood Flow Metab 8: 291–303

    Google Scholar 

  • Coenen HH, Laufer P, Stöcklin G, Wienhard K, Pawlik G, Böcher-Schwarz HG, Heiss WD (1987) 3-N-[2-(18F)-fluoroethyl]-spiperone: a novel ligand for cerebral dopamine receptor studies with PET. Life Sci 40: 81–88

    Google Scholar 

  • Coenen HH, Wienhard K, Stöcklin G, Laufer P, Hebold I, Pawlik G, Heiss WD (1988) PET measurement of D2 and S2 receptor binding of 3-N-([2′-18F]fluoroethyl)spiperone in baboon brain. Eur J Nucl Med 14: 80–87

    Google Scholar 

  • Farde L, Wiesel FA, Hall H, Halldin C, Stone-Elander S, Sedvall G (1987a) No D2 receptor increase in PET study of schizophrenia. Arch Gen Psychiatry 44: 671–672

    Google Scholar 

  • Farde L, Wiesel FA, Halldin C, Sedvall G (1987b) PET-determination of central D1- and D2-dopamine receptor occupancy in neuroleptic treated schizophrenics. In: Heiss WD, Pawlik G, Herholz K, Wienhard K (eds) Clinical efficacy of positron emission tomography. Martinus Nijhoff, Dordrecht Boston Lancaster, pp 213–219

    Google Scholar 

  • Fowler JS, Arnett CD, Wolf AP, MacGregor RR, Norton EF, Findley AM (1982) [11C]spiroperidol: synthesis, specific activity determination and biodistribution in mice. J Nucl Med 23: 437–445

    Google Scholar 

  • Garnett ES, Firnau G, Nahmias C (1983) Dopamine visualized in the basal ganglia of living man. Nature 305: 137–138

    Google Scholar 

  • Garnett ES, Nahmias C, Firnau G (1984) Central dopaminergic pathways in hemiparkinsonism examined by positron emission tomography. Can J Neurol Sci 11: 174–179

    Google Scholar 

  • Heiss WD, Pawlik G, Herholz K, Wagner R, Göldner H, Wienhard K (1984) Regional kinetic constants and CMRglu in normal volunteers determined by dynamic positron emission tomography of [18F]2-fluoro-2-deoxy-D-glucose. J Cereb Blood Flow Metab 4: 212–223

    Google Scholar 

  • Huang SC, Barrio JR, Phelps ME (1986) Neuroreceptor assay with positron emission tomography: equilibrium versus dynamic approaches. J Cereb Blood Flow Metab 6: 515–521

    Google Scholar 

  • Kiesewetter DD, Eckelman WC, Cohen RM, Finn RD, Larson SM (1986) Synthesis and D2 receptor affinities of derivatives of spiperone containing aliphatic halogens. Appl Radiat Isot 37: 1181–1188

    Google Scholar 

  • Kuhl DE, Phelps ME, Markham CH, Metter EJ, Riege WH, Winter J (1982) Cerebral metabolism and atrophy in Huntington's disease determined by18FDG and computed tomographic scan. Ann Neurol 12: 425–434

    Google Scholar 

  • Lange HW (1981) Quantitative changes of telencephalon, diencephalon and mesencephalon in Huntington's chorea, postencephalitic, and idiopathic Parkinsonism. Verh Anat Ges 75: 923–925

    Google Scholar 

  • Leenders KL, Herold S, Palmer AJ, Turton D, Quinn N, Jones T, Frackowiak RS, Marsden CD (1985) Human cerebral dopamine system measured in vivo using PET. J Cereb Blood Flow Metab 5 [Suppl]: S 517-S 518

    Google Scholar 

  • Leenders KL, Frackowiak R, Quinn N, Marsden CD (1986a) Brain energy metabolism and dopaminergic function in Hungtington's disease measured in vivo using positron emission tomography. Movement Disorders 1: 69–77

    Google Scholar 

  • Leenders KL, Palmer AJ, Quinn N, Clark JC, Firnau G, Garnett ES, Nahmias C, Jones T, Marsden CD (1986b) Brain dopamine metabolism in patients with Parkinson's disease measured with positron emission tomography. J Neurol Neurosurg Psychiatry 49: 853–856

    Google Scholar 

  • Leenders KL, Quinn N, Frackowiak RSJ, Marsden CD (1988) Brain dopaminergic system studied in patients with dystonia using positron emission tomography. In: Fahn S, et al (eds) Dystonia 2. Raven Press, New York (Advances in neurology, vol 50), pp 243–253

    Google Scholar 

  • Litton J, Bergström M, Eriksson L, Bohm C, Blomqvist G, Kesselberg M (1984) Performance study of the PC-384 positron camera system for the brain. J Comput Assist Tomogr 8: 74–87

    Google Scholar 

  • Mintun MA, Raichle ME, Kilbourn MR, Wooten GF, Welch MJ (1984) A quantitative model for the in vivo assessment of drug binding sites with positron emission tomography. Ann Neurol 15: 217–227

    Google Scholar 

  • Perlmutter JS, Larson KB, Raichle ME, Markham J, Mintun MA, Kilbourn MR, Welch MJ (1986) Strategies for in vivo measurement of receptor binding using positron emission tomography. J Cereb Blood Flow Metab 6: 154–169

    Google Scholar 

  • Phelps ME, Huang SC, Hoffman EJ, Selin C, Sokoloff L, Kuhl DE (1979) Tomographic measurement of local cerebral glucose metabolic rate in humans with [18F]2-fluoro-2-deoxy-D-glucose: validation of method. Ann Neurol 6: 371–388

    Google Scholar 

  • Reivich M, Kuhl D, Wolf A, Greenberg J, Phelps M, Ido T, Casella V, Fowler J, Hoffman E, Alavi A, Som P, Sokoloff L (1979) The [18F]fluorodeoxy-glucose method for the measurement of local cerebral glucose utilization in man. Circ Res 44: 127–137

    Google Scholar 

  • Satyamurthy N, Bida GT, Barrio JR, Luxen A, Mazziotta JC, Huang SC, Phelps ME (1986) No-carrier-added 3(2′-[18F]fluoroethyl)spiperone, a new dopamine receptorbinding tracer for positron emission tomography. Nucl Med Biol 13: 617–624

    Google Scholar 

  • Seeman P (1980) Brain dopamine receptors. Pharmacol Rev 32: 229–313

    Google Scholar 

  • Seeman P (1987) Dopamine receptors in human brain diseases. In: Creese I, Fraser CF (eds) Dopamine receptors. Alan R Liss, New York, pp 233–245

    Google Scholar 

  • Siegel GJ, Albers RW, Agranoff BW, Katzman R (1981) Basic neurochemistry, 3rd edn. Little, Brown and Company, Boston

    Google Scholar 

  • Smith M, Wolf AP, Brodie JD, Arnett CD, Barouche F, Shiue CY, Fowler JS, Russel JAG, MacGregor RR, Wolkin A, Angrist B, Rotrosen J, Peselow E (1988) Serial [18F]N-ethylspiroperidol PET studies to measure changes in antipsychotic drug D-2 receptor occupancy in schizophrenic patients. Biol Psychiatry 23: 653–663

    Google Scholar 

  • Sokoloff L, Reivich M, Kennedy C, Des Rosiers MH, Patlak CS, Pettigrew KD, Sakurada O, Shinohara M (1977) The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat. J Neurochem 28: 897–916

    Google Scholar 

  • Wagner HN Jr, Burns HD, Dannals RF, Wong DF, Langström B, Duelfer T, Frost JJ, Ravert HT, Links MJ, Rosenbloom SB, Lukas SE, Kramer AV, Kuhar MJ (1983) Imaging dopamine receptors in the human brain by positron emission tomography. Science 221: 1264–1266

    Google Scholar 

  • Wienhard K, Pawlik G, Herholz K, Wagner R, Heiss WD (1985) Estimation of local cerebral glucose utilization by positron emission tomography of [18F]2-fluoro-2-deoxy-D-glucose: a critical appraisal of optimization procedures. J Cereb Blood Flow Metab 5: 115–125

    Google Scholar 

  • Wong DF, Wagner HN, Dannals RF, Links JM, Frost JJ, Ravert HT, Wilson AA, Rosenbaum AE, Gjedde A, Douglass KH, Petronis JD, Folstein MF, Toung JKT, Burns HD, Kuhar MJ (1984) Effects of age on dopamine and serotonin receptors measured by positron emission tomography in the living human brain. Science 226: 1393–1396

    Google Scholar 

  • Wong DF, Wagner HN Jr, Tune LE, Dannals RF, Pearlson GD, Links JM, Tamminga CA, Broussolle EP, Ravert HT, Wilson AA, Toung JKT, Malat J, Williams JA, O'Tuama LA, Snyder SH, Kuhar MJ, Gjedde A (1986) Positron emission tomography reveals elevated D2 dopamine receptors in drug naive schizophrenics. Science 234: 1558–1563

    Google Scholar 

Download references

Author information

Author notes

  1. W. -D. Heiss

    Present address: Max-Planck-Institut für neurologische Forschung, Köln

Authors and Affiliations

  1. Max-Planck-Institut für neurologische Forschung, Köln

    K. Wienhard, G. Pawlik, J. Rudolf & S. Jovkar

  2. Institut für Chemie 1, Kernforschungsanlage Jülich, Jülich, Federal Republic of Germany

    H. H. Coenen, P. Laufer & G. Stöcklin

Authors
  1. K. Wienhard
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. H. H. Coenen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G. Pawlik
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. Rudolf
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. P. Laufer
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. S. Jovkar
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. G. Stöcklin
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. W. -D. Heiss
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wienhard, K., Coenen, H.H., Pawlik, G. et al. PET studies of dopamine receptor distribution using [18F]fluoroethylspiperone: findings in disorders related to the dopaminergic system. J. Neural Transmission 81, 195–213 (1990). https://doi.org/10.1007/BF01245042

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01245042

Keywords

Search

Navigation