Browse > Article

GABA Receptor Imaging  

Lee, Jong-Doo (Division of Nuclear Medicine, Department of Diagnostic Radiology, Yonsei University College of Medicine)
Publication Information
Nuclear Medicine and Molecular Imaging / v.41, no.2, 2007 , pp. 166-171 More about this Journal
Abstract
GABA is primary an inhibitory neurotransmitter that is localized in inhibitory interneurons. GABA is released from presynaptic terminals and functions by binding to GABA receptors. There are two types of GABA receptors, $GABA_{A}-receptor$ that allows chloride to pass through a ligand gated ion channel and $GABA_{B}-receptor$ that uses G-proteins for signaling. The $GABA_{A}$-receptor has a GABA binding site as well as a benzodiazepine binding sites, which modulate $GABA_{A}$-receptor function. Benzodiazepine GABAA receptor imaging can be accomplished by radiolabeling derivates that activates benzodiazepine binding sites. There has been much research on flumazenil (FMZ) labeled with $^{11}C-FMZ$, a benzodiazepine derivate that is a selective, reversible antagonist to GABAA receptors. Recently, $^{18}F-fluoroflumazenil$ (FFMZ) has been developed to overcome $^{11}C short half-life. $^{18}F-FFMZ$ shows high selective affinity and good pharmacodynamics, and is a promising PET agent with better central benzodiazepine receptor imaging capabilities. In an epileptic focus, because the GABA/benzodiazepine receptor amount is decreased, using $^{11}C-FMZ$ PET instead of $^{18}F-FDG$ PET, restrict the foci better and may also help find lesions better than high resolution MR. $GABA_{A}$ receptors are widely distributed in the cerebral cortex, and can be used as an viable neuronal marker. Therefore it can be used as a neuronal cell viability marker in cerebral ischemia. Also, GABA-receptors decrease in areas where neuronal plasticity develops, therefore, $GAB_{A}$ imaging can be used to evaluate plasticity. Besides these usages, GABA receptors are related with psychological diseases, especially depression and schizophrenia as well as cerebral palsy, a motor-related disorder, so further in-depth studies are needed for these areas.
Keywords
GABA; GABA receptor; flumazenil; epilepsy;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Kaila K. Ionic basis of $GABA_A$ receptor channel function in the nervous system. Prog Neurobiol 1994;42:489-537   DOI   ScienceOn
2 Macdonald RL, Olsen RW. $GABA_A$ receptor channels. Annu Rev Neurosci 1994;17:569-602   DOI   ScienceOn
3 Olsen RW, McCabe RT, Wamsley JK. GABAA receptor subtypes: autoradiographic comparison of GABA, benzodiazepine, and convulsant binding sites in the rat central nervous system. J Chem Neuroanat 1990;3:59-76
4 Yoon YH, Jeong JM, Kim HW, Hong SH, Lee YS, Kil HS, et al. Novel one-pot one-step synthesis of 2'-[(18)F]fluoroflumazenil (FFMZ) for benzodiazepine receptor imaging. Nucl Med Biol 2003:30:521-7   DOI   ScienceOn
5 Jibiki I, Kubota T, Fujimoto K, Yamaguchi N, Matsuda H, Hisada K. Regional relationships between focal hypofixation images in 123I-IMP single photon emission computed tomography and epileptic EEG foci in interictal periods in patients with partial epilepsy. Eur Neurol 1991;31:360-5   DOI
6 Tatsu Y, Nishigaki H, Adachi I, Matsuoka T, Ashina K, Hiraishi K, et al. [A comparison among 123I-IMP SPECT, EEG and MRI in patients with temporal lobe epilepsy]. Kaku Igaku 1994:31: 1077-84
7 Ratzliff AH, Santhakumar V, Howard A, Soltesz I. Mossy cells in epilepsy: rigor mortis or vigor mortis? Trends Neurosci 2002:25: 140-4   DOI   ScienceOn
8 Ratzliff AH, Howard AL, Santhakumar V, Osapay I, Soltesz I. Rapid deletion of mossy cells does not result in a hyperexcitable dentate gyrus: implications for epileptogenesis. J Neurosci 2004:24: 2259-69   DOI   ScienceOn
9 Olsen RW, Bureau M, Houser CR, Delgado-Escueta AV, Richards JG, Mohler H. GABA/benzodiazepine receptors in human focal epilepsy. Epilepsy Res Suppl 1992:8:383-91
10 Savic I, Persson A, Roland P, Pauli S, Sedvall G, Widen L. In-vivo demonstration of reduced benzodiazepine receptor binding in human epileptic foci. Lancet 1988;2:863-6
11 Morrell F. Varieties of human secondary epileptogenesis. J Clin Neurophysiol 1989;6:227-75   DOI
12 Yamauchi H, Kudoh T, Kishibe Y, Iwasaki J, Kagawa S. Selective neuronal damage and borderzone infarction in carotid artery occlusive disease: a 11C-flumazenil PET study. J Nucl Med 2005; 46:1973-9
13 Juhasz C, Chugani DC, Muzik O, Shah A, Shah J, Watson C, et al. Relationship of flumazenil and glucose PET abnormalities to neocortical epilepsy surgery outcome. Neurology 2001;56:1650-8   DOI   ScienceOn
14 Bormann J. Electrophysiology of $GABA_A$ and $GABA_B$ receptor subtypes. Trends Neurosci 1988;11:112-6   DOI   ScienceOn
15 Newton MR, Berkovic SF, Austin MC, Rowe CC, McKay WJ, Bladin PF. SPECT in the localisation of extratemporal and temporal seizure foci. J Neurol Neurosurg Psychiatry 1995:59:26-30   DOI
16 Chang YS, Jeong JM, Yoon YH, Kang WJ, Lee SJ, Lee DS, et al. Biological properties of 2'-[18F]fluoroflumazenil for central benzodiazepine receptor imaging. Nucl Med Biol 2005:32:263-8   DOI   ScienceOn
17 Owens DF, Kriegstein AR. Is there more to GABA than synaptic inhibition? Nat Rev Neurosci 2002;3:715-27   DOI   ScienceOn
18 Kaneko K, Sasaki M, Morioka T, Koga H, Abe K, Sawamoto H, et al. Pre-surgical identification of epileptogenic areas in temporal lobe epilepsy by 123I-iomazenil SPECT: a comparison with IMP SPECT and FDG PET. Nucl Med Commun 2006:27:893-9   DOI   ScienceOn
19 Grunder G, Siessmeier T, Lange-Asschenfeldt C, Vernaleken I, Buchholz HG, Stoeter P, et al. [$^{18}F$]Fluoroethylflumazenil: a novel tracer for PET imaging of human benzodiazepine receptors. Eur J Nucl Med 2001;28:1463-70   DOI
20 Neumann-Haefelin T, Bosse F, Redecker C, Muller HW, Witte OW. Upregulation of GABAA-receptor alpha1- and alpha2-subunit mRNAs following ischemic cortical lesions in rats. Brain Res 1999;816:234-7   DOI   ScienceOn
21 Savic I, Ingvar M, Stone-Elander S. Comparison of [11C]flumazenil and [18F]FDG as PET markers of epileptic foci. J Neurol Neurosurg Psychiatry 1993;56:615-21   DOI   ScienceOn
22 Goethals I, Van de Wiele C, Boon P, Dierckx R. Is central benzodiazepine receptor imaging useful for the identification of epileptogenic foci in localization-related epilepsies? Eur J Nucl Med Mol Imaging 2003;30:325-8   DOI   ScienceOn
23 Ben-Ari Y. Excitatory actions of gaba during development: the nature of the nurture. Nat Rev Neurosci 2002;3:728-39   DOI   ScienceOn
24 Gaiarsa JL, Caillard O, Ben-Ari Y. Long-term plasticity at GABAergic and glycinergic synapses: mechanisms and functional significance. Trends Neurosci 2002;25:564-70   DOI   ScienceOn
25 Leveque P, Sanabria-Bohorquez S, Bol A, De Volder A, Labar D, Van Rijckevorsel K, et al. Quantification of human brain benzodiazepine receptors using [$^{18}F$]fluoroethylflumazenil: a first report in volunteers and epileptic patients. Eur J Nucl Med Mol Imaging 2003;30:1630-6   DOI   ScienceOn
26 McDonald JW, Garofalo EA, Hood T, Sackellares JC, Gilman S, McKeever PE, et al. Altered excitatory and inhibitory amino acid receptor binding in hippocampus of patients with temporal lobe epilepsy. Ann Neurol 1991;29:529-41   DOI   ScienceOn
27 Szelies B, Weber-Luxenburger G, Pawlik G, Kessler J, Holthoff V, Mielke R, et al. MRI-guided flumazenil- and FDG-PET in temporal lobe epilepsy. Neuroimage 1996;3:109-18   DOI   ScienceOn
28 Juhasz C, Chugani DC, Muzik O, Watson C, Shah J, Shah A, et al. Electroclinical correlates of flumazenil and fluorodeoxyglucose PET abnormalities in lesional epilepsy. Neurology 2000;55:825-35   DOI   ScienceOn
29 Chugani DC, Muzik O, Juhasz C, Janisse JJ, Ager J, Chugani HT. Postnatal maturation of human GABAA receptors measured with positron emission tomography. Ann Neurol 2001;49:618-26   DOI   ScienceOn
30 Sood S, Chugani HT. Functional neuroimaging in the preoperative evaluation of children with drug-resistant epilepsy. Childs Nerv Syst 2006;22:810-20   DOI
31 Henry TR, Frey KA, Sackellares JC, Gilman S, Koeppe RA, Brunberg JA, et al. In vivo cerebral metabolism and central benzodiazepine-receptor binding in temporal lobe epilepsy. Neurology 1993;43:1998-2006   DOI   ScienceOn
32 Mehta AK, Ticku MK. An update on $GABA_A$ receptors. Brain Res Brain Res Rev 1999;29:196-217   DOI   ScienceOn
33 Morrell F. Secondary epileptogenesis in man. Arch Neurol 1985;42:318-35   DOI   ScienceOn
34 Schwartz-Bloom RD, Sah R. gamma-Aminobutyric acid(A) neurotransmission and cerebral ischemia. J Neurochem 2001;77: 353-71   DOI   ScienceOn