Abstract
Iodine-123-iomazenil (Iomazenil) is a ligand of central type benzodiazepine receptors for single photon emission computed tomography (SPECT). Previously we reported a simple, table look-up method for quantification of its binding potential (BP) by using two SPECT scans and calibrated standard input function with one blood sampling. This method is based on a two-compartment model (K1: influx rate constant; k2: efflux rate constant; Vd (= K1/k2): the total distribution volume corresponding BP), and requires two SPECT scans for calculating both K1 and Vd values. If the K1 value in the two-compartment model can be assumed to be constant, the radioactivity of one SPECT scan at 180 min after injection can be considered to tabulate as a function of Vd for a given K1 value and a given input function, and a table look-up procedure provides the corresponding Vd value. The purpose of this study was to develop a simple, autoradiographic method for quantification of BP by using one SPECT scan and calibrated standard input function with one blood sampling. SPECT studies were performed on 14 patients. A dynamic SPECT scan was initiated following an intravenous bolus injection of Iomazenil. A static SPECT scan was performed at 180 min after the injection. Frequent blood sampling from the brachial artery was performed on all subjects to determine the arterial input function. Simulation studies revealed that errors in calculated Vd values were around ± 10–15% for varied K1 values. A good correlation was observed between total distribution volume values calculated by three-compartment model analysis and those calculated by the present method (r = 0.90), supporting the validity of this method. The present method is simple and applicable for clinical use, and will be able to provide images of BP.
Access this article
We’re sorry, something doesn't seem to be working properly.
Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.
Similar content being viewed by others
References
Beer H-F, Blauenstein PA, Hasler PH, Delaloye B, Riccabona G, Bangerl I, et al.In vitro andin vivo evaluation of iodine-123-Ro 16-0154: A new imaging agent for SPECT investigations of benzodiazepine receptors.J Nucl Med 31: 1007–1014, 1990.
Innis RB, Zoghbi SS, Johnson EW, Woods SW, Al-Tikriti MS, Baldwin RM, et al. SPECT imaging of the benzodiazepine receptor in non-human primate brain with [123I]Ro 16-0154.Eur J Pharmacol 193: 249–252, 1991.
Innis RB, Al-Tikriti MS, Zoghbi SS, Baldwin RM, Sybirska EH, Laruelle M, et al. SPECT imaging of the benzodiazepine receptor: Feasibility ofin vivo potency measurements from stepwise displacement curves.J Nucl Med 32: 1754–1761, 1991.
Woods SW, Seibyl JP, Goddard AW, Dey HM, Zoghbi SS, Germine M, et al. Dynamic SPECT imaging after injection of the benzodiazepine receptor ligand [123I]iomazenil in healthy human subjects.Psych Res Neuroimaging 45: 67–77, 1992.
Huffelen AC, Isselt JW, Veelen CWM, Rijk PP, Bentum AM, Dive D, et al. Identification of the side of the epileptic focus with123I-Iomazenil SPECT. A comparison with18FDG-PET and ictal EEG findings in patients with medically intractable complex partial seizures.Acta Neurochir Suppl 50: 95–99, 1990.
Bartenstein P, Ludolph A, Schober O, Lottes G, Scheidhauer K, Sciuk J, et al. Benzodiazepine receptors and cerebral blood flow in partial epilepsy.Eur J Nucl Med 18: 111–118, 1991.
Schubiger PA, Hasler PH, Beer-Wohlfahrt H, Bekier A, Oettli R, Cordes M, et al. Evaluation of a multicentre study with iomazenil — a benzodiazepine receptor ligand.Nucl Med Commun 12: 569–582, 1991.
Cordes M, Henkes H, Ferstl F, Schmitz B, Hierholzer J, Schmidt D, et al. Evaluation of focal epilepsy: A SPECT scanning comparison of 123-I-iomazenil versus HM-PAO.AJNR 13: 249–253, 1992.
Johnson EW, Lanerolle NC, Kim JH, Sundaresan S, Spencer DD, Mattson RH, et al. “Central” and “peripheral” benzodiazepine receptors: Opposite changes in human epileptogenic tissue.Neurology 42: 811–815, 1992.
Owen F, Poulter M, Waddington JL, Mashal RD, Crow TJ. [3H]R05-4864 and [3H]flunitrazepam binding in kainatelesioned rat striatum and in temporal cortex of brains from patients with senile dementia of the Alzheimer type.Brain Res 278: 373–375, 1983.
Reisine TD, Wastek GJ, Speth RC, Bird ED, Yamamura HI. Alterations in benzodiazepine receptor of Huntington’s diseased human brain.Brain Res 165: 183–187, 1979.
Onodera H, Sato G, Kogure K. GABA and benzodiazepine receptors in the gerbil brain after transient ischemia: Demonstration by quantitative receptor autoradiography.J Cereb Blood Flow Metab 7: 82–88, 1987.
Sette G, Baron JC, Young AR, Miyazawa H, Tillet I, Barre L, et al.In vivo mapping of brain benzodiazepine receptor changes by PET after focal ischemia in the anesthetized baboon.Stroke 24: 2046–2058, 1993.
Al-Tikriti MS, Dey HM, Zoghbi SS, Baldwin RM, Zea-Ponce Y, Innis RB. Dual-isotope autoradiographic measurement of regional blood flow and benzodiazepine receptor availability following unilateral middle cerebral artery occlusion.Eur J Nucl Med 21: 196–202, 1994.
Hatazawa J, Satoh T, Shimosegawa E, Okudera T, Inugami A, Ogawa T, et al. Evaluation of cerebral infarction with iodine 123-iomazenil SPECT.J Nucl Med 36: 2154–2161, 1995.
Mintun MA, Raichle ME, Kilbourn MR, Wooten GF, Welch MJ. A quantitative model for thein vivo assessment of drug binding sites with positron emission tomography.Ann Neurol 15: 217–227, 1984.
Wong DF, Gjedde A, Wagner HN Jr. Quantification of neuroreceptors in the living human brain. I. Irreversible binding of ligands.J Cereb Blood Flow Metab 6: 137–146, 1986.
Wong DF, Gjedde A, Wagner HN Jr, Dannais RF, Douglass KH, Links JM, et al. Quantification of neuroreceptors in the living human brain. II. Inhibition studies of receptor density and affinity.J Cereb Blood Flow Metab 6: 147–153, 1986.
Farde L, Eriksson L, Blomquist G, Halldin C. Kinetic analysis of central [11C]raclopride binding to D2-dopamine receptors studied by PET — A comparison to the equilibrium analysis.J Cereb Blood Flow Metab 9: 696–708, 1989.
Blomqvist G, Pauli S, Farde L, Eriksson L. Maps of receptor binding parameters in the human brain — a kinetic analysis of PET measurements.Eur J Nucl Med 16: 257–265, 1990.
Koeppe RA, Holthoff VA, Frey KA, Kilbourn MR, Kuhl DE. Compartmental analysis of [11C]flumazenil kinetics for the estimation of ligand transport rate and receptor distribution using positron emission tomography.J Cereb Blood Flow Metab 11: 735–744, 1991.
Holthoff VA, Koeppe RA, Frey KA, Paradise AH, Kuhl DE. Differentiation of radioligand delivery and binding in the brain: Validation of a two-compartment model for [11C]flumazenil.J Cereb Blood Flow Metab 11: 745–752, 1991.
Price JC, Mayberg HS, Dannals RF, Wilson AA, Ravert HT, Sadzot B, et al. Measurement of benzodiazepine receptor number and affinity in humans using tracer kinetic modeling, positron emission tomography, and [11C]flumazenil.J Cereb Blood Flow Metab 13: 656–667, 1993.
Laruelle M, Baldwin RM, Rattner Z, Al-Tikriti MS, Zea-Ponce Y, Zoghbi SS, et al. SPECT quantification of [123I]iomazenil binding to benzodiazepine receptors in non-human primates: I. Kinetic modeling of single bolus experiments.J Cereb Blood Flow Metab 14: 439–452, 1994.
Laruelle M, Abi-Dargham A, Al-Tikriti MS, Baldwin RM, Zea-Ponce Y, Zoghbi SS, et al. SPECT quantification of [123I]iomazenil binding to benzodiazepine receptors in nonhuman primates: II. Equilibrium analysis of constant infusion experiments and correlation within vitro parameters.J Cereb Blood Flow Metab 14: 453–465, 1994.
Abi-Dargham A, Laruelle M, Seibyl J, Rattner Z, Baldwin RM, Zoghbi SS, et al. SPECT measurement of benzodiazepine receptors in human brain with iodine-123-iomazenil: Kinetic and equilibrium paradigms.J Nucl Med 35: 228–238, 1994.
Abi-Dargham A, Gandelman M, Zoghbi SS, Laruelle M, Baldwin RM, Randall P, et al. Reproducibility of SPECT measurement of benzodiazepine receptors in human brain with iodine-123-iomazenil.J Nucl Med 36: 167–175, 1995.
Onishi Y, Yonekura Y, Mukai T, Nishizawa S, Tanaka F, Okazawa H, et al. Simple quantification of benzodiazepine receptor binding and ligand transport using iodine-123-iomazenil and two SPECT scans.J Nucl Med 36: 1201–1210, 1995.
Huang SC, Barrio JR, Phelps ME. Neuroreceptor assay with positron emission tomography. Equilibrium versus dynamic approaches.J Cereb Blood Flow Metab 6: 515–521, 1986.
Lassen NA. Neuroreceptor quantitationin vivo by the steady-state principle using constant infusion or bolus injection of radioactive tracers.J Cereb Blood Flow Metab 12: 709–716, 1992.
Ito H, Goto R, Koyama M, Kawashima R, Ono S, Sato K, et al. A simple method for the quantification of benzodiazepine receptors using iodine-123 iomazenil and singlephoton emission tomography.Eur J Nucl Med 23: 782–791, 1996.
Iida H, Itoh H, Bloomfield PM, Munaka M, Murakami M, Inugami A, et al. A method to quantitate cerebral blood flow using a rotating gamma camera and iodine-123 iodoamphetamine with one blood sampling.Eur J Nucl Med 21: 1072–1084, 1994.
Itoh H, Iida H, Murakami M, Bloomfield PM, Miura S, Okudera T, et al. A method for measurement of regional cerebral blood flow using N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) SPECT; two scans with one point blood sampling technique.KAKU IGAKU (Jpn J Nucl Med) 29: 1193–1200, 1992.
Ito H, Koyama M, Goto R, Kawashima R, Ono S, Atsumi H, et al. Cerebral blood flow measurement with iodine-123-IMP SPECT, calibrated standard input function and venous blood sampling.J Nucl Med 36: 2339–2342, 1995.
Ito H, Ishii K, Atsumi H, Kinoshita T, Kawashima R, Ono S, et al. Error analysis of table look-up method for cerebral blood flow measurement by123I-IMP brain SPECT: Comparison with conventional microsphere model method.Ann Nucl Med 9: 75–80, 1995.
Zoghbi SS, Baldwin RM, Seibyl JP, Al-Tikriti MS, Zea-Ponce Y, Lamelle M, et al. Pharmacokinetics of the SPECT benzodiazepine receptor radioligand [123I]iomazenil in human and non-human primates.Nucl Med Biol 19: 881–888, 1992.
Kimura K, Hashikawa K, Etani H, Uehara A, Kozuka T, Moriwaki H, et al. A new apparatus for brain imaging: fourhead rotating gamma camera single-photon emission computed tomography.J Nucl Med 31: 603–609, 1990.
Chang LT. A method for attenuation correction in radionuclide computed tomography.IEEE Trans Nucl Sci 25: 638–643, 1978.
Chang LT. Attenuation correction and incomplete projection in single photon emission computed tomography.IEEE Trans Nucl Sci 26: 2780–2789, 1979.
Renkin EM. Transport of potassium-42 from blood to tissue in isolated mammalian skeletal muscles.Am J Pkysiol 197: 1205–1210, 1959.
Crone C. Permeability of capillaries in various organs as determined by use of the indicator diffusion method.Acta Physiol Scand 58: 292–305, 1963.
Neider JA, Mead R. A simplex method for function minimization.Computer J 7: 308–312, 1965.
Koeppe RA, Mangner T, Betz AL, Shulkin BL, Allen R, Kollros P, et al. Use of [11C]aminocyclohexanecarboxylate for the measurement of amino acid uptake and distribution volume in human brain.J Cereb Blood Flow Metab 10: 727–739, 1990.
Onishi Y, Yonekura Y, Nishizawa S, Tanaka F, Okazawa H, Ishizu K, et al. Noninvasive quantification of iodine-123-iomazenil SPECT.J Nucl Med 37: 374–378, 1996.
Ito H, Ishii K, Atsumi H, Inukai Y, Abe S, Sato M, et al. Error analysis of autoradiography method for measurement of cerebral blood flow by123I-IMP brain SPECT: A comparison study with table look-up method and microsphere model method.Ann Nucl Med 9: 185–190, 1995.
Iida H, Itoh H, Nakazawa M, Hatazawa J, Nishimura H, Onishi Y, et al. Quantitative mapping of regional cerebral blood flow using iodine-123-IMP and SPECT.J Nucl Med 35: 2019–2030, 1994.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ito, H., Kawashima, R., Koyama, M. et al. A method for the quantification of benzodiazepine receptors by using123I-iomazeniI and SPECT with one scan and one blood sampling. Ann Nucl Med 11, 101–108 (1997). https://doi.org/10.1007/BF03164817
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF03164817