Skip to main content
Log in

Maps of receptor binding parameters in the human brain — a kinetic analysis of PET measurements

  • Original Article
  • Published:
European Journal of Nuclear Medicine Aims and scope Submit manuscript

Abstract

A kinetic method is described for the estimation of neuroreceptor density as well as the rate constants for association and dissociation of rapidly equilibrating radioligands. The method is exemplified by positron emission tomographic measurements of the human brain using11C-raclopride, a D 2 dopamine receptor antagonist, and11C-Ro 15-1788, a benzodiazepine receptor antagonist. Using a linear non iterative algorithm, regional binding characteristics were calculated and displayed pixel by pixel in brain maps. Data from repeated experiments on the same subject with different amounts of the unlabeled ligand were utilized. The binding characteristics were determined according to a two step procedure in which the time course of the free radioligand concentration was estimated from a reference region considered to be free of specific receptor binding sites. Alternative methods to determine the concentration of free radioligand are discussed.

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

Access this article

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

  • Bergström M, Boethius J, Eriksson L, Greitz T, Ribbe T, Widen L (1981) A head fixation device for reproducible alignment in transmission CT and positron emission tomography. J Comput Assist Tomogr 5:136–141

    Google Scholar 

  • Blomqvist G (1984) On the construction of functional maps in positron emission tomography. J Cereb Blood Flow Metabol 4:629–632

    Google Scholar 

  • Beck JV, Arnold KJ (1977) Parameter estimation in engineering and science. Wiley, New York, pp 192–204

    Google Scholar 

  • Eckernäs S-Å, Aquilonius SM, Hartwig P, Hägglund J, Lundqvist H, Någren K, Långström B (1987) Positron emission tomography (PET) in the study of dopamine receptors in the primate brain: evaluation of a kinetic model using C11-N-methyl-spiperone. Acta Neurol Scand 75:168–178

    Google Scholar 

  • Farde L, Ehrin E, Eriksson L, Greitz T, Hall H, Sedvall G (1985) [11C]labelled dopamine-D2 receptor antagonists as tools for quantitative studies on dopamine receptors in the human brain. J Cerebr Blood Flow Metabol 5:(S1) 595–596

    Google Scholar 

  • Farde L, Hall H, Ehrin E, Sedvall G (1986) Quantitative analysis of D2 dopamine receptor binding in the living human brain by PET. Science 231:258–261

    Google Scholar 

  • Farde L, Pauli S, Hall H, Eriksson L, Halldin C, Högberg T, Nilsson L, Sjögren I, Stone-Elander S (1988) Stereoselective binding of C11-raclopride — a search for extrastriatal central D2-dopamine receptors by PET. Psychopharmacology 94:471–478

    Google Scholar 

  • Huang S-C, Barrio JR, Phelps ME (1986) Neuroreceptor assay with positron emission tomography: Equilibrium versus dynamic approaches. J Cereb Blood Flow Metabol 6:515–521

    Google Scholar 

  • Logan J, Wolf AP, Shiue C-Y, Fowler JS (1987) Kinetic modeling of receptor-ligand binding applied to positron emission tomographic studies with neuroleptic tracers. J Neurochem 48:73–83

    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 M, Kilbourn R, Welch W (1986) Strategies for in vivo measurements of receptor binding using positron emission tomography. J Cereb Blood Flow Metabol 6:154–169

    Google Scholar 

  • Persson A, Pauli S, Halldin C, Stone-Elander S, Farde L, Sjögren I, Sedvall G (1989) Saturation analysis of specific11C Ro15-1788 binding to the human neocortex using positron emission tomography. Human Psychopharmacology 4:21–31

    Google Scholar 

  • Toga AW, Santori E, Samaie M (1986) Regional distribution of flunitrazepam binding constants:Kd andB max by digital analysis. J Neurosci 6:274–275

    Google Scholar 

  • Wong DF, Gjedde A, Wanger HN Jr (1986) Quantification of neuroreceptors in the living human brain. I. Irreversible binding of ligands. J Cereb Blood Flow Metabol 6:137–146

    Google Scholar 

  • Yamamura H (1985) Neurotransmitter receptor binding. Raven, New York

    Google Scholar 

  • Yamasaki T, Inoue O, Shinotoh H, Itch T, Iyo M, Tateno Y, Suzuki K, Kashida Y, Hashimoto K, Tadokoro H (1986) Benzodiazepine receptor study in the elderly using PET and clinical application of a new tracer, C-11-methyl N-methyl benzyl amine. Liver and aging. In: Kitani K (ed) Liver and brain. Elsevier, Amsterdam, pp 265–276

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Blomqvist, G., Pauli, S., Farde, L. et al. Maps of receptor binding parameters in the human brain — a kinetic analysis of PET measurements. Eur J Nucl Med 16, 257–265 (1990). https://doi.org/10.1007/BF00842777

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00842777

Key words

Navigation