Abstract
Using positron emission tomography (PET), the distribution and binding of radiolabelled ligands can be studied in the human brain in vivo (Comar et al., 1979). This technique has been applied for the study of dopamine (Wagner et al., 1983; Farde et al., 1989), benzodiazepine (Persson et al., 1985), and muscarinic acetylcholine (Frey et al., 1992) receptors. The development of methods for synthesis of radiolabelled nicotine (Mazière et al., 1976; Halldin et al.1992) made it possible to study brain uptake and distribution of this alkaloid by PET in animals (Ohno et al., 1976) and man (Nybäck et al., 1989; 1993). Although a diminished brain uptake of [11C]-nicotine has been found in Alzheimer patients as compared to healthy subjects (Nordberg et al., 1991), it has not been demonstrated that this decline is due to loss of specific nicotinic receptors. The decline may as well be brought about by general tissue loss and decreased cerebral blood flow associated with the degenerative disease process. The recent development of substituted thiadiazole-methylpyridines (TZTP) as specific M1 muscarinic agonists and their labelling with [11C] (Halldin et al., 1993) has offered new possibilities for treatment attempts and for diagnostic imaging of neurodegenerative disorders.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Bartus, R.T., Dean III, R.L., Beer, B., and Lippa, A.S., 1982, The cholinergic hypothesis of geriatric memory dysfunction, Science 217: 408.
Comar, D., Mazièr, M., Godot, J.M., Berger, G., Soussaline, F., Menini, C., Arfel, G., and Naquet, R., 1979, Visualization of “C-flunitrazepam displacement in the brain of the live baboon, Nature 280: 1184.
Farde, L., Eriksson, L., Blomqvist, G., and Halldin, C., 1989, 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.
Ferris, S.H., DeLeon, M.J., Wolf, A.P., Farkas, T., Christman, D.R., Reisberg, B., Fowler, J., MacGregor R., Goldman, A., George, A.E., and Rampal, S., 1980, Positron emission tomography in the study of aging and senile dementia, Neurobiol. Aging 1: 127.
Foster, N.L., Chase, T.N., Fedio, P., Patronas, N.J., Brooks, R.A., and DiChiro, G., 1983, Alzheimer’s disease: Focal cortical changes shown by positron emission tomography, Neurol 33: 961.
Frey, K.A., Koeppe, R.A., Mulholland, G.K., Jewett, D., Hichwa, R., Ehrenkaufer, R.L.E., Carey, J.E., Wieland, D.M., Kuhl, D.E., and Agranoff, B.W., 1992, In vivo muscarinic cholinergic receptor imaging in human brain with [11C]-scopolamine and positron emission tomography, J Cereb Blood Flow Metab 12: 147.
Halldin, C., NAgren, K., Swahn, C-G., LAngström, B., and Nybäck, H., 1992, (S)- and (R)-[11C]-nicotine and the metabolite (R/S)-[”C]cotinine. Preparation, metabolite studies and in vivo distribution in the human brain using PET, Nucl. Med. Biol. 19: 871.
Halldin, C., Miller, L., Foged, C., Sauerberg, P., Karlsson, P., Swahn, C-G., Hall, H., and Farde, L., 1993, Preparation of three carboni 1 labelled novel functional MI selective muscarinic agonists, J. Nucl. Med. (in press).
Larsson, C., and Nordberg A., 1985, Comparative analysis of nicotine-like receptor-ligand interactions in rodent brain homogenate, J. Neurochem. 45: 24.
Litton, J., Bergström, M., Eriksson, L., Bohm, C., Blomqvist, G., and Kesselberg, M., 1984, Performance study of the PC-384 positron camera system for emission tomography of the brain, J. Comput. Assist. Tomogr. 8: 74.
Litton, J.E., Holte, S., and Eriksson, L., 1990, Evaluation of the Karolinska new positron camera system; the Scanditronix PC2048–15B, IEEE Transact. Nucl. Sci. 37: 743.
Mazière, M., Comar, D., Marazano, C., and Berger, G„ 1976, Nicotine-“C: Synthesis and distribution kinetics in animals, Eur. J. Nucl. Med. 1: 255.
Nordberg, A., and Winblad, B., 1986, Reduced number of ell)-nicotine and (’H)-acetylcholine binding sites in the frontal cortex of Alzheimer brains, Neurosci. Lett. 72: 115.
Nordberg, A., Hartvig, P., Lilja, A., Viitanen, M., Amberla, K., Lundqvist, H., Ulin, J., Andersson, Y., LAngström, B., and Winblad, B., 1991, Brain nicotinic receptor deficits in Alzheimer patients as studied by positron emission tomography, in: “Alzheimer’s Disease: Basic Mechanisms, Diagnosis and Therapeutic Strategies,” K. Iqbal, D.R. McLachlan, B. Winblad, H.M. Wisniewski, eds, Wiley, Chichester New York Toronto Singapore, pp 517.
Nybäck, H., Nordberg, A., LAngström, B., Halldin, C., Hartvig, P., Ahlin, A., Swahn, C-G., and Sedvall, G., 1989, Attempts to visualize nicotinic receptors in the brain of monkey and man by positron emission tomography, Progr. Brain Res. 79: 313.
Nybäck, H., Nyman, H., Blomqvist, G., Sjögren, I., and Stone-Elander, S., 1991, Brain metabolism in Alzheimer’s dementia: Studies of “C-deoxyglucose accumulation, CSF mono-amine metabolites and neuropsychological test performance in patients and healthy subjects, J. Neurol. Neurosurg. Psychiat. 54: 672.
Nybäck, H., Halldin, C., Ahlin, A., Curvall, M., and Eriksson, L., 1993, PET studies of the uptake of (S)-and (R)-[11C]nicotine in the human brain: Difficulties in visualizing specific receptor binding in vivo, Psychopharmacology (in press).
Ohno, K., Pettigrew, KD., and Rapoport, S.I., 1979, Local cerebral blood flow in the conscious rat as measured with 14C-antipyrine, 14C-iodoantipyrine and ‘H-nicotine, Stroke 10: 62.
Olson, L., Nordberg, A., von Holst, H., Bäckman, L., Ebendal, T., Alafuzoff, I, Amberla, K., Hartvig, P., Herlitz, A., Lilja, A., Lundqvist, H., LAngström, B., Meyerson, B., Persson, A., Viitanen, M., Winblad, B., and Seiger, A., 1992, Nerve growth factor affects “C-nicotine binding, blood flow, EEG, and verbal episodic memory in an Alzheimer patient (Case report), J. Neural. Transm. [P-D Sect] 4: 79.
Persson, A., Elwin, E., Eriksson, L., Farde, L., Hedström, C-G., Litton, J-E., Mindus, P., and Sedvall, G., 1985, Imaging of [11C]-labelled RO 15–1788 binding to benzodiazepine receptors in the human brain by positron emission tomography, J. Psychiat. Res. 19: 609.
Saji, H., Magata, Y., Yamada, Y., Tajima, K., Yonekura, Y., Konishi, J., Ohmomo, Y., and Yokoyama, A., 1992, Synthesis of (S)-N-[methyl-“C]nicotine and its regional distribution in mouse brain: A potential tracer for visualization of brain nicotinic receptors by positron emission tomography, Chem. Pharm. Bull. 40: 734.
Sedvall, G., Farde, L., Persson, A., and Wiesel, F-A., 1986, Imaging of neurotransmitter receptors in the living human brain, Arch. Gen. Psychiat. 43: 995.
Wagner, H.N., Bums, Jr, H.D., Dannals, R.F., Wong, D.F., LAngström, B., Duelfer, T., Frost, J.J., Ravert, H.T., Links, J.M., Rosenbloom, S.B., Lukas, S.E., Kramer, A.V., and Kuhar, M.J. (1983) Imaging dopamine receptors in the human brain by positron tomography, Science 221: 1264.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1995 Springer Science+Business Media New York
About this chapter
Cite this chapter
Nybäck, H. et al. (1995). Positron Emission Tomography (PET) Studies with Ligands for Cholinergic Receptors in the Human Brain. In: Hanin, I., Yoshida, M., Fisher, A. (eds) Alzheimer’s and Parkinson’s Diseases. Advances in Behavioral Biology, vol 44. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-9145-7_37
Download citation
DOI: https://doi.org/10.1007/978-1-4757-9145-7_37
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4757-9147-1
Online ISBN: 978-1-4757-9145-7
eBook Packages: Springer Book Archive