Imaging Neuroreceptors with Positron Emission Tomography: A New Strategy for Measuring Pharmacological Activity in the Treatment of Schizophrenia

  • J. D. Brodie
  • S. L. Dewey
  • A. P. Wolf
  • G. S. Smith


Among the major problems which must be faced in the study of schizophrenia is the lack of an objective set of biological discriptors which can be used to define the syndrome and thus the response to treatment. The advent of positron emission tomography (PET) in the early 1970s offered a new opportunity to directly visualize aspects of cerebral function. PET is a medical imaging technique which measures the concentration of a positron emitting radioisotope in a volume element of tissue. When an appropriately radiolabeled ligand is used, PET provides functional images of the target tissue. Interpretation of these images in a meaningful way is dependent upon an understanding of the underlying biochemistry and physiology of the tissue and characterization of the binding of the radioligand. This involves a knowledge of the process to be traced and the kinetics of that process, since the tomograph only measures but does not attach biological significance to radioactive events.


Positron Emission Tomography Cholinergic Receptor Cereb Blood Flow Positron Tomography Positron Emission Tomography Ligand 
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  1. Bartlett EJ, Brodie JD, Wolf AP, Christman DR, Laska E, Meissner M (1988) Reproducibility of cerebral glucose metabolic measurements in resting human subjects. J Cereb Blood Flow Metab 8:502–512PubMedCrossRefGoogle Scholar
  2. Buchsbaum MS, Ingvar DH, Kessler R, Waters RN, Cappelletti J, van Kammen DP, King AC, Johnson JL, Manning RG, Flynn RW, Mann LS, Bunney WE Jr, Sokoloff L (1982) Cerebral glucography with positron tomography: use in normal subjects and in patients with schizophrenia. Arch Gen Psychiatry 39:251–259PubMedGoogle Scholar
  3. Cambon H, Baron JC, Boulenger JP, Loc’h C, Zarifian E, Maziere B (1987) In vivo assay for neuroleptic receptor binding in the striatum. Positron tomography in humans. Br J Psychiatry 151:824PubMedCrossRefGoogle Scholar
  4. Coyle JT, Snyder SH (1969) Antiparkinsonian drugs: inhibition of dopamine uptake in the corpus striatum as a possible mechanism of action. Science 166:809–811CrossRefGoogle Scholar
  5. DeLisi LE, Holcomb HH, Cohen RM, Pickar D, Carpenter W et al. (1985) Positron emission tomography in schizophrenic patients with and without neuroleptic medication. J Cereb Blood Flow Metab 5:201–206PubMedCrossRefGoogle Scholar
  6. Dewey SL, Wolf AP, Fowler JS, Brodie JD, Shiue C-Y, Alavi A, Hiesiger E, Schlyer DJ, Volkow ND, Raulli R, Christman D (1988) The effects of central cholinergic blockade on [I8F]-N-methylspiroperidol binding in human brain using PET. XVI CINP CongressGoogle Scholar
  7. Dewey SL, MacGregor RR, Brodie JD, Bendriem B, King PT, Volkow ND, Schlyer DJ, Fowler JS, Wolf AP, Gatley SJ, Hitzeman R (1990a) Mapping muscarine receptors in human and baboon brain using [N-13C-methyl]benztropine. Synapse 5:213–223PubMedCrossRefGoogle Scholar
  8. Dewey SL, Brodie JD, Fowler JS, MacGregor RR, Schlyer DJ, King PT, Alexoff DL, Volkow ND, Shiue C-Y, Wolf AP, Bendriem B (1990b) Positron emission tomography (PET) studies of dopaminergic/cholinergic interactions in the baboon brain. Synapse 6:321–327PubMedCrossRefGoogle Scholar
  9. Farde L, Ehrin E, Eriksson L, Greitz TY, Hall H, Hedstrom CG, Litton JE, Sedvall G (1985) Substituted benzamides as ligands for visualization of dopamine receptor binding in the human brain by positron emission tomography. Proc Natl Acad Sci USA 82:3863PubMedCrossRefGoogle Scholar
  10. Farde L, Wiesel F-A, Halldin C, Sedvall G, Nilsson L (1989) Dopamine receptor occupancy and plasma haloperidol levels: in reply. Arch Gen Psychiatry 46: 483–4Google Scholar
  11. Farkas T, Wolf AP, Fowler J, MacGregor R, Brodie JD, Christman D, Cancro R, Brill R, Goldman A (1981) Regional brain glucose metabolism in schizophrenia. J Cereb Blood Flow Metabol 1 [Suppl 1]:496Google Scholar
  12. Farkas T, Wolf AP, Jaeger J, Brodie JD, Christman D, Fowler JS (1984) Regional brain glucose metabolism in chronic schizophrenia. Arch Gen Psychiatry 41:293–300PubMedGoogle Scholar
  13. Gur RE, Resnick SM, Gur RC, Alavi A, Caroff S, Kushner M, Reivich M (1987) Regional brain function in schizophrenia. Arch Gen Psychiatry: 44:119–125PubMedGoogle Scholar
  14. McGeer PL, Eccles JC, McGeer EG (1987) Molecular neurobiology of the mammalian brain. Plenum, New YorkGoogle Scholar
  15. Seeman P, Guan H-C, Nizik HB (1989) Endogenous dopamine lowers the dopamine D2 receptor density as measured by [3H]raclopride: implications for positron tomography of the human brain. Synapse 3:96–97PubMedCrossRefGoogle Scholar
  16. Smith M, Wolf AP, Brodie JD, Arnett CD, Barouche F, Shiue CY, Fowler JS, Russell JAG, MacGregor RR, Wolkin A, Angrist B, Rotrosen J, Peselow E (1988) Serial 18F-N-Methylspiroperidol PET studies to measure changes in antipsychotic drug D2 receptor occupancy in schizophrenic patients. Biol Psychiatry 23:653–663PubMedCrossRefGoogle Scholar
  17. Szechtman H, Nachmias C, Garnett ES, Firnaue G, Brown GM, Kaplan RD, Cleghorn JM (1988) Effects of neuroleptics on altered cerebral glucose metabolism in schizophrenia. Arch Gen Psychiatry 45:523–532PubMedGoogle Scholar
  18. Tyler JL, Strother SZ, Zatorre RJ, Alivisatos B, Worsley KJ, Diksie M, Yamamoto YL (1988) Stability of regional cerebral glucose metabolism in the normal human brain measured by positron emission tomography. J Nucl Med 29:631PubMedGoogle Scholar
  19. Wagner HN Jr, Burns HD, Dannals RF, Wong DF, Langstrom B, Duelfer T, Frost JJ, Ravert HT, Links JM, Rosenbloom SB, Lukas SE, Kramer AV, Kuhar MJ (1983) Imaging dopamine receptors in the human brain by positron tomography. Science 221:1264–1266PubMedCrossRefGoogle Scholar
  20. Wolkin A, Jaeger J, Brodie JD, Wolf AP, Fowler J, Rotrosen J, Gomez-Mont F, Cancro R (1985) Peristence of cerebral metabolic abnormalities in chronic schizophrenia as determined by positron emission tomography. Am J Psychiatry 142:564–571PubMedGoogle Scholar
  21. Wolkin A, Brodie JD, Barouche F, Rotrosen J, Wolf AP, Cooper T (1989a) Dopamine receptor occupancy and plasma haloperidol levels. Arch Gen Psychiatry 46:482–483PubMedGoogle Scholar
  22. Wolkin A, Barouche F, Wolf AP, Rotrosen J, Fowler JS, Shiue CY, Cooper TB, Brodie JD (1989b) Dopamine blockade and clinical response: evidence for two biological subgroups of schizophrenia. Am J Psychiatry 146:905–908PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1993

Authors and Affiliations

  • J. D. Brodie
    • 1
  • S. L. Dewey
  • A. P. Wolf
  • G. S. Smith
  1. 1.Dept. of PsychiatryNew York University Medical CenterNew York, NYUSA

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