Skip to main content
Log in

Dopamine D2 receptor SPECT imaging: Basicin vivo characteristics and clinical applications of123I-IBZM in humans

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

Abstract

The purposes of this study are to evaluate the utility of kit formulation, the basicin vivo characteristics, and clinical usefulness of dopamine D2 receptor imaging with123I-(S)-(-)-3-iodo-2-hydroxy-6-methoxy-N-[(1-ethyl-2-pyrrodinyl)methyl]-benzamide (123I-IBZM). We studied 22 normal controls, 3 early symptomatic Huntington’s disease patients, and 1 patient with visual hallucination on and off neuroleptics.123I-IBZM could be conveniently prepared with a high degree of purity from a kit, but with relatively low radiochemical yield. We demonstrated123I-IBZM receptor binding equilibrium by performing serial SPECT scanning in a normal volunteer. The basal ganglia/frontal cortex (BG/FC) ratios plateaued after the specific binding reached equilibrium approximately 60 minutes after injection. The BG/FC ratio declined significantly with age. The ratios for the Huntington’s disease patients were significantly lower than those for normal controls. The images of the patient off neuroleptic therapy showed dramatically increased BG activity compared with those obtained while on therapy. The BG/FC ratio provides an estimate of Bmax/Kd and hence the receptor density. It appears important to perform SPECT early in the equilibrium phase and at a fixed time after injection to obtain significantly high signal to noise ratios.123I-IBZM is an ideal tracer for SPECT including a rotating gamma camera type which can provide estimates of the receptor density objectively by calculating the BG/FC ratio, and is a promising agent for the investigation of dopamine D2 receptors in clinical conditions.

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

  1. Verhoeff NPLG: Pharmacological implications for neuroreceptor imaging.Eur J Nucl Med 18: 482–502, 1991

    Article  PubMed  CAS  Google Scholar 

  2. Baron JC, Mazière B, Loc’h C, et al: Loss of striatal [76Br] bromospiperone binding sites demonstrated by positron tomography in progressive supranuclear palsy.J Cereb Blood Flow Metab 11: 220–228, 1991

    Google Scholar 

  3. Budinger TF: Advances in emission tomography: Quo vadis? [Editorial]J Nucl Med 31: 628–631, 1990

    PubMed  CAS  Google Scholar 

  4. Kung HF, Pan S, Kung MP, et al:In vitro andin vivo evaluation of [123I]IBZM: A potential CNS D-2 dopamine receptor imaging agent.J Nucl Med 30: 88–92, 1989

    PubMed  CAS  Google Scholar 

  5. Brücke T, Tsai YF, Mclellan C, et al:In vitro binding properties and autoradiographic imaging of 3-iodobenzamide ([125I]-IBZM): A potential imaging ligand for D-2 dopamine receptors in SPECT.Life Sci 42: 2097–2104, 1988

    Article  PubMed  Google Scholar 

  6. Kung HF, Alavi A, Chang W, et al:In vivo SPECT imaging of CNS D-2 dopamine receptors: Initial studies with iodine-123-IBZM in humans.J Nucl Med 31: 573–579, 1990

    PubMed  CAS  Google Scholar 

  7. Costa DC, Verhoeff NPLG, Cullum ID, et al:In vivo characterization of 3-iodo-6-methoxybenzamide123I in humans.Eur J Nucl Med 16: 813–816, 1990

    Article  PubMed  CAS  Google Scholar 

  8. Brücke T, Podreka I, Angelberger P, et al: Dopamine D2 receptor imaging with SPECT: Studies in different neuropsychiatric disorders.J Cereb Blood Flow Metab 11: 220–228, 1991

    PubMed  Google Scholar 

  9. Verhoeff NPLG, Brücke T, Podreka I, et al: Dynamic SPECT in two healthy volunteers to determine the optima] time forin vivo D2 dopamine receptor imaging with123I-IBZM using the rotating gamma camera.Nucl Med Commun 12: 687–697, 1991

    Article  PubMed  CAS  Google Scholar 

  10. Mazière B, Loc’h C, Raynaud C, et al: I-123 Iodolisuride, a new SPECT imaging ligand for brain dopamine D2 receptors [Abstract].J Nucl Med 30: 731–732, 1989

    Google Scholar 

  11. Yonekura Y, Iwasaki Y, Saji H, et al: SPECT imaging of dopamine D-2 receptor: Kinetics of I-123 2′iodospiperone in normal subjects [Abstract].J Nucl Med 31: 885, 1990

    Google Scholar 

  12. Kung MP, Kung HF, Billings J, et al: The characterization of IBF as a new selective dopamine D-2 receptor imaging agent.J Nucl Med 31: 648–654, 1990

    PubMed  CAS  Google Scholar 

  13. Ichise M, Toyama H, Fornazzari L, et al: Assessment of subjects with and at risk for developing Huntington’s disease by I-123 IBZM and Tc-99m HM-PAO SPECT [Abstract].J Nucl Med 33: 970, 1992

    Google Scholar 

  14. Tatsch K, Schwarz J, Oertel WH, et al: SPECT imaging of dopamine D2 receptors with123I-IBZM: Initial experience in controls and patients with Parkinson’s syndrome and Wilson’s disease.Nucl Med Commun 12: 699–707, 1991

    Article  PubMed  CAS  Google Scholar 

  15. Kung MP, Liu BL, Yang YY, et al: A kit formulation for preparation of iodine-123-IBZM: A new CNS D-2 dopamine receptor imaging agent.J Nucl Med 32: 339–342, 1991

    PubMed  CAS  Google Scholar 

  16. Farde L, Hall H, Ehrin E, et al: Quantitative analysis of D2 dopamine receptor binding in living human brain by PET.Science 231: 258–261, 1986

    Article  PubMed  CAS  Google Scholar 

  17. Farde L, Eriksson L, Blomquist G, et al: Kinetic analysis of central [11C]raclopride binding to D2-dopamine receptors studied by PET—A comparison to the equation analysis.J Cereb Blood Flow Metab 9: 696–708, 1989

    PubMed  CAS  Google Scholar 

  18. Sedvall G, Farde L, Persson A, et al: Imaging of neurotransmitter receptors in the living human brain.Arch Gen Psychiatry 43: 995–1005, 1986

    PubMed  CAS  Google Scholar 

  19. Kebabian JW, Calne DB: Multiple receptors for dopamine.Nature 277: 93–96, 1979

    Article  PubMed  CAS  Google Scholar 

  20. Bunzow JR, Van Tol HHM, Grandy DK, et al: Cloning and expression of a rat D2 dopamine receptor cDNA [Letter].Nature 336: 783–787, 1988

    Article  PubMed  CAS  Google Scholar 

  21. Giros B, Sokoloff P, Martes MP, et al: Alternative splicing directs the expression of two D2 dopamine receptor isoforms [Letter].Nature 342: 923–926, 1989

    Article  PubMed  CAS  Google Scholar 

  22. Monsma FJ, McVittie LD, Gerfen CR, et al: Multiple D2 dopamine receptors produced by alternative RNA splicing [Letter].Nature 342: 926–929, 1989

    Article  PubMed  CAS  Google Scholar 

  23. Dal Toso R, Sommer B, Ewert M, et al: The dopamine D2 receptor: two molecular forms generated by alternative splicing.EMBO J 8: 4025–4034, 1989

    Google Scholar 

  24. Sokoloff P, Giros B, Martres MP, et al: Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics.Nature 347: 146–151, 1990

    Article  PubMed  CAS  Google Scholar 

  25. Van Tol HHM, Bunzow JR, Guan HC, et al: Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine [Letter].Nature 350: 610–614, 1991

    Article  PubMed  Google Scholar 

  26. Sunahara RK, Guan HC, O’Dowd BF, et al: Cloning of the gene for a human dopamine D5 receptor with higher affinity for dopamine than D1 [Letter].Nature 350: 614–619, 1991

    Article  PubMed  CAS  Google Scholar 

  27. Beaulieu M: Clinical importance of D-1 and D-2 receptors.Can J Neurol Sci 14: 402–406, 1987

    PubMed  CAS  Google Scholar 

  28. Wagner HN, Burns HD, Dannais RF, et al: Imaging dopamine receptors in the human brain by positron tomography.Science 221: 1264–1266, 1983

    Article  PubMed  CAS  Google Scholar 

  29. Crawley JCW, Smith T, Veall N, et al: Dopamine receptors displayed in living human brain with77Brp-bromospiperone.Lancet 2: 975, 1983

    Article  PubMed  CAS  Google Scholar 

  30. Seeman P, Niznik HB, Guan HC: Elevation of Dopamine D2 receptors in schizophrenia is underestimated by radioactive raclopride [Letter].Arch Gen Psychiatry 47: 1170–1172, 1990

    PubMed  CAS  Google Scholar 

  31. Misra CH, Shelat HS, Smith RC: Effect of age on adrenergic and dopaminergic receptor binding in rat brain.Life Sci 27: 521–526, 1980

    Article  PubMed  CAS  Google Scholar 

  32. Marquis JK, Lippa AS, Pelham RW: Dopamine receptor alterations with aging in mouse and rat corpus striatum.Biochem Pharmacol 30: 1876–1878, 1981

    Article  PubMed  CAS  Google Scholar 

  33. Severson JA, Marcusson J, Winbland B, et al: Agecorrelated loss of dopaminergic binding sites in human basal ganglia.J Neurochem 39: 1623–1631, 1982

    Article  PubMed  CAS  Google Scholar 

  34. Morgan DG, Marcusson JA, Nyberg P, et al: Divergent changes in D-1 and D-2 dopamine binding sites in human brain during aging.Neurobiol Aging 8: 195–201, 1987

    Article  PubMed  CAS  Google Scholar 

  35. Guttman M, Seeman P: Dopamine D2 receptor density in Parkinsonian brain is constant for duration of disease, age, and duration of L-dopa therapy.Adv Neurol 45: 51–57, 1986

    Google Scholar 

  36. Brooks DJ, Ibanez V, Sawle GV, et al: Striatal D2 receptor status in patients with Parkinson’s disease, Striatonigral degeneration, and Progressive supranuclear palsy, measured with11C-raclopride and positron emission tomography.Ann Neurol 31: 184–192, 1992

    Article  PubMed  CAS  Google Scholar 

  37. Seeman P, Guan HC, Niznik HB: Endogenous dopamine lowers the dopamine D2 receptor density as measured by [3H]raclopride: Implications for positron emission tomography of the human brain.Synapse 3: 96–97, 1989

    Article  PubMed  CAS  Google Scholar 

  38. Young LT, Wong DF, Goldman S, et al: Effects of endogenous dopamine on kinetics of [3H]N-methylspiperone and [3H]raclopride binding in the rat brain.Synapse 9: 188–194, 1991

    Article  PubMed  CAS  Google Scholar 

  39. Innis RB, Malison RT, Tikriti MAL, et al: Amphetamine-stimulated dopamine release competesin vivo for [123I]IBZM binding to the D2 receptor in nonhuman primates.Synapse 10: 177–184, 1992

    Article  PubMed  CAS  Google Scholar 

  40. Wong DF, Wagner HN, Dannals RF, et al: Effects of age on dopamine and serotonin receptors measured by positron tomography in the living human brain.Science 226: 1393–1396, 1984

    Article  PubMed  CAS  Google Scholar 

  41. Iyo M, Yamasaki T, Fukuda H, et al: Age-related decrease of11C-N-methylspiperonein vivo binding to human striatum detected by PET.Kaku Igaku 26: 213–220, 1989

    PubMed  CAS  Google Scholar 

  42. Thal LJ, Horowitz SG, Dvorkin B, et al: Evidence for loss of brain [3H]spiroperidol and [3H]ADTN binding sites in rabbit brain with aging.Brain Res 192: 185–194, 1980

    Article  PubMed  CAS  Google Scholar 

  43. Leenders KL, Frackowiak RSJ, Quinn N, et al: Brain energy metabolism and dopaminergic function in Huntington’s disease measuredin vivo using positron emission tomography.Movement disorders 1: 69–77, 1986

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Toyama, H., Ichise, M., Ballinger, J.R. et al. Dopamine D2 receptor SPECT imaging: Basicin vivo characteristics and clinical applications of123I-IBZM in humans. Ann Nucl Med 7, 29–38 (1993). https://doi.org/10.1007/BF03164789

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03164789

Key words

Navigation