Abstract
To establish a quantitative single-photon emission tomography (SPET) procedure for imaging CNS D2 dopamine receptors, measurement of unchanged iodine-123 iodobenzamide (123I-IBZM) (a selective D2 ligand) in human plasma was investigated. There are three possible radioactive components in human plasma: hydrophilic compounds (iodide ion, etc.), lipophilic metabolites, and unchanged IBZM. Based on the difference in lipophilicity of IBZM and its lipophilic metabolites (LM), a new quantitative method of analysis of 123I-IBZM using a simple solvent extraction was developed. The selective extraction was achieved with n-octane/phosphate buffer (0.1 M, pH 7.4). Extraction efficiency was 93.2% ± 0.3% (n=15) for IBZM from plasma, while 99.3% ± 0.2% (n =12) of LM remained in the aqueous plasma fraction. Twenty-one confirmation tests with plasma containing known ratios of IBZM/LM, ranging between 0.39 and 7.60, were performed. The experimental results were very close to the values of the true ratios over the wide range (accuracy ∼ 99%, relative standard error 6.6%). The data from this simplified method are comparable to those obtained by the high-performance liquid chromatography method. This improved method provides an easy and accurate way to quantify unchanged IBZM in human plasma. With appropriate kinetic modeling and in conjunction with a dedicated SPET imaging device for measuring quantitative information, it may be possible to develop a practical method for measuring D2 receptor density in vivo.
Similar content being viewed by others
References
Martres MP, Sales N, Bouthenet ML, Schwartz JC. Localization and pharmacological characterization of D-2 dopamine receptors in rat cerebral neoxortex and cerebellum using [125I]iodosulpiride. Eur J Pharmacol 1985; 118:211–219.
Janowsky A, De Paulis T, Clanton J, Smith H, Ebert M, Kessler R. [125I]Iodopride: a specific high affinity radioligand for labelling striatal dopamine D-2 receptors. Eur J Pharmacol 1988; 150:203–205.
Kung HF, Kasliwal R, Pan S, Kung MP, Mach R, Guo YZ. Dopamine D-2 receptor imaging radiopharmaceuticals: synthesis, radiolabeling, and in vitro binding of (R)-(+)- and (S)-(−)-3-iodo-2-hydroxy-6-methoxy-N-[1-ethyl-2-pyrrolidinylmethyl]benzamide. J Med Chem 1988; 31:1039–1043.
Kung MP, Liu BL, Yang YY, Billings J, Kung HF. A kit formulation for preparation of iodine-123-IBZM: a new CNS D-2 dopamine receptor imaging agent. J Nucl Med 1991; 32:339–342.
Hall H, Högberg T, Halldin C, Köhler C, Ström P, Ross S, Larsson S, Farde L. NCQ 298, a new selective iodinated salicylamide ligand for the labelling of dopamine D2 receptors. Psychopharmacology 1991; 103:6–18.
Kessler RM, Ansari M, de Paulis T, Schmidt D, Clanton J, Smith HE, Manning R, Gillespie D, Ebert MH. High affinity dopamine D2 receptor radioligands. 1. Regional rat brain distribution of iodinated benzamides. J Nucl Med 1991; 32:1593–1600.
Kessler RM, Ansari M, Schmidt D, de Paulis T, Clanton J, Innis R, Al-Tikriti M, Manning R, Gillespie D. High affinity dopamine D2 receptor radioligands. 2. [125I]Epidepride, a potent and specific radioligand for the characterization of striatal and extrastriatal dopamine D2 receptors. Life Sci 1991; 49:617–628.
Sánchez-Roa P, Grigoriadis D, Wilson A, Sharkey J, Dannals R, Villemagne V, Wong D, Wagner H Jr, Kuhar M. [125]I- Spectramide: a novel benzamide displaying potent and selective effects at the D2 dopamine receptor. Life Sci 1989; 45:1821–1829.
Kung MP, Kung HF, Billings J, Yang Y, Murphy R, Alavi A. The characterization of IBF as a new selective dopamine D-2 receptor imaging agent. J Nucl Med 1990; 31:648–654.
Costa D, Verhoeff N, Cullum I, Ell P, Syed G, Barrett J, Palazidou E, Toone B, Van Royen E, Bobeldijk M. In vivo characterization of 3-iodo-6-methoxybenzamide 123I in humans. Eur J Nucl Med 1990; 16:813–816.
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. Dynamic SPECT imaging of dopamine D2 receptors in human subjects with iodine-123-IBZM. J Nucl Med 1992; 33:1964–1971.
Cordes M, Henkes H, Laudahn D, Bräu H, Kramp W, Girke W, Hierholzer J, Eichstädt H, Felix R. Initial experience with SPECT examinations using [123I]IBZM as a D2-dopamine receptor antagonist in Parkinson's disease. Eur J Radiol 1991; 12:182–186.
Gearney DP, Ellis PM, Soper N, Shepstone BJ, Cowen PJ. Single photon emission tomography assessment of cerebral dopamine D2 receptor blockade in schizophrenia. Biol Psychiatry 1992; 32:293–295.
Schwarz J, Tatsch K, Vogel T, Kirsch CM, Trenkwalder C, Arnold G, Gasser T, Oertel WH. Marked reduction of striatal dopamine D2 receptors as detected by 123IBZM-SPELT in a Wilson's disease patient with generalized dystonia. Mov Disord 1992; 7:58–61.
Schwarz J, Tatsch K, Arnold G, Gasser T, Trenkwalder C, Kirsch CM, Oertel WH (1992) 123I-Iodobenzamide-SPECT predicts dopaminergic responsiveness in patients with de novo parkinsonism. Neurology 1992; 42:556–561.
Pilowsky LS, Costa DC, Ell PJ, Murray RM, Verhoeff NPLG, Kerwin RW. Clozapine, single photon emission tomography, and the D2 dopamine receptor blockade hypothesis of schizophrenia. Lancet 1992; 340:199–202.
Gawell L, Hagberg C-E, Högberg T, Widman M. Synthesis of 5-substituted 5-hydroxy-2-pyrrolidones, metabolites of the antipsychotic benzamide remoxipride. Acta Chem Scand 1989; 43:476–480.
Swahn C-G, Halldin C, Lundstrom J, Erixson E, Farde L. A rapid and efficient HPLC-method for determination of liquid metabolism during PET-studies - Exemplified with [11C]raclopride [abstract]. International Symposium on Radiopharmaceutical Chemistry, F17
De Jesus O, Tokars M, Van Moffaert G, Chen Y, Woolverton W, Cooper M. Characterization of C-11-SCH 23390 and its possible metabolites in primate blood using high performance liquid chromatography. J Radioanal Nucl Chem 1988; 125:65–73.
Kung HF, Alavi A, Chang W, Kung MP, Keyes J Jr, Velchik M, Billings J, Pan S, Noto R, Rausch A, Reilley J. In vivo SPELT imaging of CNS D-2 dopamine receptors: initial studies with iodine-123-IBZM in humans. J Nucl Med 1990; 31:573–579.
Author information
Authors and Affiliations
Additional information
Correspondence to: Mei-Ping T. Kung
Rights and permissions
About this article
Cite this article
Guo, YZ., Kung, MP.T., Cheng, H. et al. A simplified method for quantitation of iodine-123 iodobenzamide in human plasma: a technical note. Eur J Nucl Med 20, 373–378 (1993). https://doi.org/10.1007/BF00208994
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00208994