Abstract
The majority of drugs and other organic compounds that are considered foreign to the body undergoes metabolic changes in vivo. Most drugs are metabolized by a system of enzymes of low substrate specificity requirement which is present mainly in the liver but drug metabolism may also take place in the kidneys and lungs. The various products obtained by the metabolism are identified in terms of concentrations and kinetics. Drug metabolism has been described as a detoxication of potentially harmful substances from the environment. This is not strictly true since the resulting products and metabolites can also be toxic. Drugs can undergo many different types of biochemical reactions, which can be divided into four main types, namely, oxidations, reductions, hydrolysis and synthesis. Radiopharmaceuticals are like any other drugs or compounds liable to chemical transformation after their administration in vivo to humans. For radiopharmaceuticals we are only concerned with the parent compound and its radioactive metabolites [1].
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
Maziere B, Cantineau R, Coenen HH, Guillaume M, Halldin C, Luxen A, Loch C, Luthra SK. PET radiopharmaceutical metabolism - plasma metabolite analysis. In: Stöcklin G, Pike VW, editors. Radiopharmaceuticals for positron emission tomography. Methodological aspects. Kluwer, 1993; 151–178.
Halldin C, Stone-Elander S, Farde L, Ehrin E, Fasth K-J, Långström B, Sedvall G. Preparation of 11C-labelled SCH 23390 for the in vivo study of dopamine D-1 receptors using positron emission tomography. Appl Radiat Isot 1986;37:1039–1043.
Farde L, Halldin C, Stone-Elander S, Sedvall G. Analysis of human dopamine receptor subtypes using 11C-SCH 23390 and 11C-raclopride. Psychopharmacol 1987;92:278–284.
Sedvall G, Karlsson P, Lundin A, Anvret M, Suhara T, Halldin C, Farde L. Dopamine Dl receptor number - a sensitive PET marker for early brain degeneration in Huntington’s disease. Eur J Clinical Neurosci 1993; 243:249–255.
Farde L, Nordström A-L, Wiesel F-A, Pauli S, Halldin C, Sedvall G. PET-analysis of central D1- and d2-dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine - relation to extrapyramidal side effects. Arch Gen Psychiatry 1992;49:538–544.
DeJesus OT, Tokars ML, Van Moffaert GJC, Chen YW, Woolverton WL, Cooper MD. 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.
Swahn C-G, Farde L, Halldin C, Sedvall G. Ligand metabolites in plasma during PET-studies with the 11C-labelled dopamine antagonists, raclopride, SCH 23390 and N-methylspiroperidol. Hum Psychopharmacol 1992;7:97–103.
Halldin C, Någren K, Långström B, Swahn C-G, Nybäck H. (R/S)-[11C]cotinine, (S)-[11C]nicotine and (R)-[11C]nicotine. Preparation, metabolite studies and in vivo distribution in the human brain using PET. J Nucl Med 1991; 19:871–880.
Swahn CG, Halldin C, Farde L, Sedvall G. Metabolism of the PET ligand [11C]SCH 23390. Identification of two radiolabeled metabolites with HPLC. Human Psychopharmacology 1994;9:25–31.
Halldin C, Farde L, Barnett A, Sedvall G. Synthesis of carbon-11 labelled SCH 39166, a new selective dopamine D-l receptor ligand, and prelininary PET investigations. Appl Radiat Isot 1991;42:451–455.
Halldin C, Foged C, Farde L, Karlsson P, Hansen K, Gronvald F, Swahn C-G, Hall H, and Sedvall G. [11C]NNC 687 and [11C]NNC 756, dopamine D-1 receptor ligands. Preparation, autoradiography and PET investigation in monkey. Nucl Med Biol 1993; 20:945–953.
Swahn C-G, Halldin C, Farde L, Karlsson P, Sedvall G. Metabolism in human plasma determined by HPLC for five 11C-labelled benzazepines-radioligands for PET examination of the dopamine D-l receptor. J Labelled Compd Radiopharm 1994;35:540–542.
Karlsson P, Farde L, Halldin C, Swahn C-G, Sedvall G, Foged C, Hansen K, Skrumsager B. PET examination of [11C]NNC 687 and [11C]NNC 756 as new radioligands for the Dl-dopamine receptor. Psychopharmacology 1993; 113:149–156.
Karlsson P, Sedvall G, Halldin C, Swahn C-G, Farde L. Evaluation of SCH 39166 as a PET ligand for D1 -dopamine receptor binding and occupancy in healthy men. Psychopharmacology (in press 1995).
Halldin C, Farde L, Högberg T, Hall H, Ström P, Ohlberger A, Solin O. A comparative PET-study of five carbon-11 or fluorine-18 labelled salicylamides. Preparation and in vitro dopamine D-2 receptor binding. Nucl Med Biol 1991; 18: 871–881.
Farde L, Hall H, Ehrin E, Sedvall G. Quantitative analysis of dopamine D2 receptor binding in the living human brain by positron emission tomography. Science 1986;231:258–261.
Swahn C-G, Halldin C, Lundström J, Erixon E, Farde L. A rapid and efficient HPLC-method for determination of ligand metabolism during PET-studies -examplified with [11C]raclopride. J Labelled Compd Radiopharm 1993;32:284–285.
Widman M, Nilsson LB, Bryske B, Lundström J. Disposition of remoxipride in different species. Species differences in metabolism. Arzneim-Forsch/Drug Res 1993;43:287–297.
Maziere M, Hantraye P, Prenant C. Sastre J, Comar D. Synthesis of ethyl 8-fluoro-5,6-dihydro-5-[11C]methyl-6-oxo-4H-imidazo[l,5 a][l,4]benzo- diazepine-3-carboxylate (Ro 15-1788-11C): A specific radioligand for the in vivo study of central benzodiazepine receptors by positron emission tomography. Int J Appl Radiatlsot 1984;35:973–976.
Ehrin E, Johnström P, Stone-Elander S, Nilsson JLG, Persson A, Farde L, Sedvall G, Litton J-E, Eriksson L, Widen L, Greitz T.Preparation and preliminary positron emission tomography studies of uC-Ro 15-1788, a selective benzodiazepine receptor antagonist. Acta Pharm Suec 1984;21:183–188.
Suzuki K, Inoue O, Hashimoto K, Yamasaki T, Kuchiki M, Tamate K. Computer-controlled large scale production of high specific activity [11C]Ro 15-1788 for PET studies of benzodiazepine receptors. Int J Appl Radiat Isot 1985;36:971–976.
Halldin C, Stone-Elander S, Thorell J-O, Persson A, Sedvall G. 11C-Labelling of Ro 15-1788 in two different positions, and also 11C-labelling of its main metabolite Ro 15-3890, for PET studies of benzodiazepine receptors. Appl Radiat Isot 1988; 39:993–997.
Frost JJ, Wagner HN. (1991) Quantitative imaging. Raven Press 1991;118.
Swahn C-G, Persson A, Pauli S, Sedvall G. Metabolism of the benzodiazepine antagonist 11C-Ro 15-1788 after intravenous administration in man. Hum Psychopharmacol 1989;4:297–301.
Persson A, Pauli S, Swahn C-G, Halldin C, Sedvall G. Cerebral uptake of 11C-Ro 15-1788 and its acid metabolite 11C-Rp 15-3890; PET study in healthy volunteers. Hum Psychopharmacol 1989;4:215–220.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1995 Springer Science+Business Media Dordrecht
About this chapter
Cite this chapter
Halldin, C., Swahn, CG., Farde, L., Sedvall, G. (1995). Radioligand Disposition and Metabolism — Key Information in Early Drug Development. In: Comar, D. (eds) PET for Drug Development and Evaluation. Developments in Nuclear Medicine, vol 26. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-0429-6_5
Download citation
DOI: https://doi.org/10.1007/978-94-011-0429-6_5
Publisher Name: Springer, Dordrecht
Print ISBN: 978-94-010-4191-1
Online ISBN: 978-94-011-0429-6
eBook Packages: Springer Book Archive