Dynamic SPECT imaging of dopamine D2 receptors in human subjects with iodine-123-IBZM

J. P. Seibyl, S. W. Woods, S. S. Zoghbi, R. M. Baldwin, H. M. Dey, A. W. Goddard, Y. Zea- Ponce, G. Zubal, M. Germine, E. O. Smith, G. R. Heninger, D. S. Charney, H. F. Kung, A. Alavi, P. B. Hoffer, R. B. Innis

Research output: Contribution to journalArticle

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Abstract

We studied the uptake, distribution, metabolism and washout of the dopamine D2 receptor ligand [123I]IBZM in healthy subjects (n = 12) with dynamic brain SPECT. The highest radioactivity level was detected in the striatum. Operationally-defined striatal 'specific' uptake peaked at 69 min postinjection of radioligand and showed a gradual decline of 15% per hour thereafter. 'Specific' uptake at maximal counts represented 53% of the total striatal radioactivity. Two subjects received haloperidol (20 μg/kg i.v.) 80 min postinjection of radioligand. Haloperidol caused a 2.6-fold increase in the rate of washout of specific striatal activity in comparison to that in the 10 control subjects and was consistent with drug-induced displacement of radioligand from the dopamine D2 receptor. Two classes of metabolites were detected in plasma and urine: a polar fraction, not extracted by ethyl acetate, and a nonpolar, extractable fraction consisting of parent compound and two compounds having shorter retention times on reversed-phase HPLC. Greater than half the plasma parent was metabolized within 10-15 min after administration. The volume of distribution, estimated from the peak arterial plasma concentration at 50-75 sec, was 7.7-10.21; the free (nonprotein bound) fraction of [123I]IBZM after in vitro incubation with blood or plasma was 4.4% ± 0.4%. These results suggest that [123I]IBZM exhibits uptake in brain regions with high D2 receptor density and shows a relatively stable washout during which drugs affecting dopaminergic transmission may be administered.

Original languageEnglish (US)
Pages (from-to)1964-1971
Number of pages8
JournalJournal of Nuclear Medicine
Volume33
Issue number11
StatePublished - 1992
Externally publishedYes

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Single-Photon Emission-Computed Tomography
Corpus Striatum
Iodine
Dopamine D2 Receptors
Haloperidol
Radioactivity
Dopamine Agents
Brain
Healthy Volunteers
High Pressure Liquid Chromatography
Urine
Ligands
3-iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2-pyrrolidinyl)methyl)benzamide
human DRD2 protein
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology

Cite this

Seibyl, J. P., Woods, S. W., Zoghbi, S. S., Baldwin, R. M., Dey, H. M., Goddard, A. W., ... Innis, R. B. (1992). Dynamic SPECT imaging of dopamine D2 receptors in human subjects with iodine-123-IBZM. Journal of Nuclear Medicine, 33(11), 1964-1971.

Dynamic SPECT imaging of dopamine D2 receptors in human subjects with iodine-123-IBZM. / Seibyl, J. P.; Woods, S. W.; Zoghbi, S. S.; Baldwin, R. M.; Dey, H. M.; Goddard, A. W.; Zea- Ponce, Y.; Zubal, G.; Germine, M.; Smith, E. O.; Heninger, G. R.; Charney, D. S.; Kung, H. F.; Alavi, A.; Hoffer, P. B.; Innis, R. B.

In: Journal of Nuclear Medicine, Vol. 33, No. 11, 1992, p. 1964-1971.

Research output: Contribution to journalArticle

Seibyl, JP, Woods, SW, Zoghbi, SS, Baldwin, RM, Dey, HM, Goddard, AW, Zea- Ponce, Y, Zubal, G, Germine, M, Smith, EO, Heninger, GR, Charney, DS, Kung, HF, Alavi, A, Hoffer, PB & Innis, RB 1992, 'Dynamic SPECT imaging of dopamine D2 receptors in human subjects with iodine-123-IBZM', Journal of Nuclear Medicine, vol. 33, no. 11, pp. 1964-1971.
Seibyl JP, Woods SW, Zoghbi SS, Baldwin RM, Dey HM, Goddard AW et al. Dynamic SPECT imaging of dopamine D2 receptors in human subjects with iodine-123-IBZM. Journal of Nuclear Medicine. 1992;33(11):1964-1971.
Seibyl, J. P. ; Woods, S. W. ; Zoghbi, S. S. ; Baldwin, R. M. ; Dey, H. M. ; Goddard, A. W. ; Zea- Ponce, Y. ; Zubal, G. ; Germine, M. ; Smith, E. O. ; Heninger, G. R. ; Charney, D. S. ; Kung, H. F. ; Alavi, A. ; Hoffer, P. B. ; Innis, R. B. / Dynamic SPECT imaging of dopamine D2 receptors in human subjects with iodine-123-IBZM. In: Journal of Nuclear Medicine. 1992 ; Vol. 33, No. 11. pp. 1964-1971.
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AU - Seibyl, J. P.

AU - Woods, S. W.

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AU - Dey, H. M.

AU - Goddard, A. W.

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AU - Germine, M.

AU - Smith, E. O.

AU - Heninger, G. R.

AU - Charney, D. S.

AU - Kung, H. F.

AU - Alavi, A.

AU - Hoffer, P. B.

AU - Innis, R. B.

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N2 - We studied the uptake, distribution, metabolism and washout of the dopamine D2 receptor ligand [123I]IBZM in healthy subjects (n = 12) with dynamic brain SPECT. The highest radioactivity level was detected in the striatum. Operationally-defined striatal 'specific' uptake peaked at 69 min postinjection of radioligand and showed a gradual decline of 15% per hour thereafter. 'Specific' uptake at maximal counts represented 53% of the total striatal radioactivity. Two subjects received haloperidol (20 μg/kg i.v.) 80 min postinjection of radioligand. Haloperidol caused a 2.6-fold increase in the rate of washout of specific striatal activity in comparison to that in the 10 control subjects and was consistent with drug-induced displacement of radioligand from the dopamine D2 receptor. Two classes of metabolites were detected in plasma and urine: a polar fraction, not extracted by ethyl acetate, and a nonpolar, extractable fraction consisting of parent compound and two compounds having shorter retention times on reversed-phase HPLC. Greater than half the plasma parent was metabolized within 10-15 min after administration. The volume of distribution, estimated from the peak arterial plasma concentration at 50-75 sec, was 7.7-10.21; the free (nonprotein bound) fraction of [123I]IBZM after in vitro incubation with blood or plasma was 4.4% ± 0.4%. These results suggest that [123I]IBZM exhibits uptake in brain regions with high D2 receptor density and shows a relatively stable washout during which drugs affecting dopaminergic transmission may be administered.

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