Abstract
In the past several years our group has synthesized a series of high affinity iodine-123 and fluorine-18 labeled substituted benzamide ligands for SPECT and PET visualization of the dopamine D-2 receptors in brain regions with low receptor density outside the striatum. Radioiodination and radiofluorination in high yield and high specific activity was achieved by using the tributyltin precursor and nucleophilic displacement of the toluensulfonyl ester precursor, respectively.
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References
Kiesewetter, D.O.; Brucke, T.; Finn, R.D. Radiochemical Synthesis of [18F] Fluororaclopride. Appl. Radiat. Isot. 1989, 40,455–460.
Fukumura, T.; Dohmoto, H.; Maeda, M.; Fukuzawa, E.; Kojima, M. Synthesis and in vitro Affinity for Dopamine D-2 Receptor of N-Fluorine-Substituted Analogs of Eticlopride. Chem.. Pharm. Bull. 1990, 38, 1740–1742.
Mukherjee, J., Luh, K. E.; Yasillo, N.; Perry B.D.; Levy, D.; Chen, C-T.; Ortega, C., Beck, R. N.; Cooper, M. Dopamine D-2 Receptors Imaged by PET in Cebus apella Using [18F] Benzamide Neuroleptic. Eur J. Pharm. 1990, 175, 363–364.
Mukherjee, J.; Perry, B.D.; Cooper, M. Fluorinated Benzamide Neuroleptics. J Labelled Cmpnds.and Radiopharm. 1990, 28, 609–616.
Kiesewetter, D.O.; Kawai, R.; Chelliah M.; Owens, E.; McLellan, C; Blasberg, R.G. Preparation and Biological Evaluation of 18F-labeled Benzamide Analogs as Potential Dopamine D2 Receptor Ligands. Int. J. Radiat. Appl. Instrum. 1990, 17, 347–356.
Gerdes, J. M.; Bishop, J. E.; Mathis, C. A. Fluoroalkybenzenes: Synthesis of (S)-2.3-Dimethoxy-5-[(3-fluoro)propyl]-6-hydroxy-N-[(l-ethyl-2-pyrrolidinyl) methyl] benzamide. J. Fluorine Chem. 1991, 51, 149–152.
Hall, H.; Hogberg, T.; Halldin, C; Bengtsson, S.; Wedel, I. Synthesis and Binding Properties of the Fluorinated Substituted Benzamide [3H]NCQ 115, a New Selective Dopamine D2 Receptor Ligand. Eur. J. Pharmacol. 1991, 201, 1–10.
Halldin, C.; Farde L.; Hogberg, T.; Hall, H.; Strom, 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.
Mukherjee, J. Fluorinated Benzamide Neuroleptics—2. Synthesis and Radiosynthesis of (S)-N-[(l-ethyl-2-pyrrolidinyl)methyl]-5-(3-[18F]fluoropropyl)-3-substituted- 2-methoxy- benzamides. Appl. Radiat. Isot. 1991, 42, 713–721.
Mukherjee, J. Fluorinated Benzamide Neuroleptics—2. Synthesis and Radiosynthesis of (S)-N-[(l-ethyl-2-pyrrolidinyl)methyl]-5-(3-[18F]fluoropropyl)-3-substituted- 2-methoxy- benzamides. Appl. Radiat. Isot. 1991, 42, 713–721f.
Watanabe, K.; Fukumura, T.; Sasaki, S.; Maeda, M.; Takehara S. New Fluorine- Substituted Analogue of Eticlopride with High Affinity Toward Dopamine D2 Receptors. Chem. Pharm. Bull. 1991, 39, 3211–3214.
Mathis, C. A.; Bishop, J. E., Gerdes, J. M.; Whitney, J.M., Brennam, K.M., and Jagust, W.J.. Synthesis and Evaluation of High Affinity, Aryl-substituted [18F]Fluoropropylbenzamides for Dopamine D-2 Receptor Studies. Nucl. Med. Biol. 1992, 19,571–588.
13. Chumpradit, S.; Kung, M.P.; Billings, J.; Mach R.; Kung. H.F. Fluorinated and Iodinated Dopamine Agents: D2 Imaging Agents for PET and SPECT. J. Med. Chem. 1992.
Sasaki, S.; Takao, F.; Watanabe, K.; Obana, N.; Maeda, M.; Fukumura, T.; Takehara, S. New Fluorinated Dopamine D2 Ligands with Benzofuran Skeleton. The Synthesis and in Vitro Evaluation. Chem. Pharm. Bull. 1993, 41, 296–300.
Kessler, R. M.; Votaw, J. R.; Schmidt, D.E.; Ansari, M.S.; Holdeman, K.P.; de Paulis, T.; Clanton, J.A.; Pfeffer, R.; Manning, R.G.; Ebert, M.H. High Affinity Dopamine D2 Receptor Radioligands. 3. [123I] and [125I]Epidepride: In Vivo Studies in Rhesus Monkey Brain and Comparison with In Vitro Pharmacokinetics in Rat Brain. Life Sciences 1993,53,241–250.
Kung, H. F.; Kasliwal, R.; Pan, S.; Kung M-P.; Mach, R. H.; Guo, Y-Z. 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- pyrrolidinyl)methyl] benzamide. J. Med. Chem. 1988, 31, 1039–1043.
de Paulis, T.; Janowsky, A.; Kessler, R.M.; Clanton, J.A.; Smith H.E. (S)-N-[(l- Ethyl- 2-pyrrolidinyl)methyl]-5-[125I]iodo-2-methoxybenzamide Hydrochloride, a New Selective Radioligand for Dopamine D-2 Receptors. J. Med. Chem. 1988, 31,2027–2033.
Kung, H.F.; Pan, S.; Kung, M-P.; Billings, J.; Kasliwal, R.; Reilley, J.; Alavi, A. In Vitro and In Vivo Evaluation of [123I]IBZM: A Potential CNS D-2 Dopamine Receptor Imaging Agent. J. Nucl. Med. 1989, 30, 88–92.
Sanchez-Roa, P.M.; Grigoriadis, D.E.; Wilson, A.A.; Sharkey, J.; Dannais, R.F.; Villemagne, V.L.; Wong, D.F.; Wagner, H.N. Kuhar, M.J.; [125]I-Spectramide: A Novel Benzamide Displaying Potent and Selective Effects at the D2 Dopamine Receptor. Life Sci. 1989,45,1821–1829.
Hogberg, T.; Strom, P.; Hall, H.; Kohler, G; Halldin, G; Farde, L. Syntheses of [123I]-, [125T]- and Unlabelled (S)-3-iodo-5,6-dimethoxy-N-[l-ethyl-2- pyrrolidinyl) methyl] salicylamide (NCQ 298), Selective Ligands for the Study of Dopamine D-2 Receptors. Acta. Pharm. Nord. 1990, 1, 53–60.
Murphy, R.A.; Kung, H.F.; Kung, M-P.; Billings, J. Synthesis and Characterization of Iodobenzamide Analogues: Potential D-2 Dopamine Receptor Imaging Agents. J. Med. Chem. 1990, 33, 171–178.
Hogberg, T de Paulis, T.; Johansson, L.; Kumar, Y.; Hall, H.; Ogren, S.O..; Potential Antipsychotic Agents. 7. Synthesis and Antidopamingergic Properties of the Atypical Highly Potent (S)-5-Bromo-2,3-dimethoxy-N-[(l-ethyl-2-pyrrolidinyl) methyl]benzamide and Related Compounds. A Comparative Study. J. Med. Chem. 1990, 33, 2305–2309.
Kessler, R.M.; Ansari, M.S de Paulis, T.; Schmidt, D.E.; Clanton Smith, H.E.; Manning, R.G.; Gillespie, D.; Ebert, M.H..; High Affinity Dopamine D2 Receptor Radioligands. 1. Regional Rat Brain Distribution of Iodinated Benzamides. J. Nucl. Med. 1991, 32, 1593–1600.
Clanton, J.A de Paulis, T., Schmidt, D.E., Ansari, M.S.; Manning, R.G.; Baldwin, R.M.; Kessler, R.M..; Preparation of [123I]- and [125I]Epidepride: A Dopamine D-2 Receptor Antagonist Radioligand. J. Label Cmpnd Radiopharma 1991, 29, 745–751.
de Paulis, T.; Bingham, D.R.; Manning, R.G.; Mason, N.S.; Ansari, M.S.; Schmidt, D.E.; Kessler, R. M. Design and Radiogluorination of Benzamide Dopamine D2 Receptor Ligands. New Trends in Radiopharmaceutical Synthesis, Quality Assurance, and Regulatory Control 1991, 97–107.
Kessler, R.M.; Ansari, M.S.; Schmidt de Paulis, T.; Clanton, J.A.; Innis, R.; Al- Tikriti, M.; Manning, R.G.; Gillespie, D., D.E.; 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.
Kessler, R.M.; Whetsell, W.O.; Ansari, M.S.; Votaw, J.R de Paulis, T.; Clanton, J.A.; Schmidt, D.E.; Mason, N.S.; Manning, R.G..; Identification of Extrastriatal Dopamine D2 Receptors in Post Mortem Human Brain with [125I]Epidepride. Brain Res. 1993, 609, 237–243.
Kessler, R.M.; Mason, N.S.; Votaw, J.R de Paulis, T.; Clanton, J.A.; Ansari, M.S.; Schmidt, D.E.; Manning, R.G.; Bell, R.L..; Visualization of Extrastriatal Dopamine D-2 Receptors in the Human Brain. Eur. J. Pharmacol. 1992, 223, 105–107.
Kessler, R.M.; Votaw, J.R de Paulis, T.; Bingham, D.R.; Ansari, M.S.; Mason, N.S.; Holburn, G.; Schmidt, D.E.; Votaw, D.B.; Manning, R.G.; Ebert, M.H..; Evaluation of 5-[18F]Fluoropropylepidepride as a Potential PET Radioligand for Imaging Dopamine D2 Receptors. Synapse 1993,15,169–176.
Neve, K.A.; Henningsen, R.A.; Kinzie, J.M de Paulis, T.; Schmidt, D.E.; Kessler, R.M.; Janowsky, A..; Sodium-Dependent Isomerization of Dopamine D-2 Receptors Characterized Using [125I]Epidepride, a High-Affinity Substituted Benzamide Ligand. J. Pharmacol. Exp. Ther. 1990, 252, 1108–1116.
Kung, H.F.; Alavi, A.; Chang, W.; Kung, M-P.; Keyes, J.W.; Velchik, M.G.; Billings, J.; Pan, S.; Noto, R.; Rausch, A.; Reilley, J. In Vivo SPECT Imaging of CNS D-2 Dopamine Receptors: Initial Studies with Iodine- 123-IBZM in Humans. J. Nucl. Med. 1990,31,573–579.
Kung, M-P.; Kung, H.F.; 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.
Brucke, T.; Podreka, I.; Angelberger, P.; Wenger, S.; Topitz, A.; Kufferle, B.; Müller, C; Deecke, L. Dopamine D2 Receptor Imaging with SPECT: Studies in Different Neuropsychiatric Disorders. J. Cereb. Blood Flow Metab 1991, 11, 220–228.
Verhoeff, N.P.L.G.; Bobeldijk, M.; Feenstra, M.G.P.; Boer, G.J.; Maas, M.A.W.; Erdtsieck-Ernste, E.; De Bruin, K. Van Royen, E.A.; In Vitro and In Vivo D2- Dopamine Receptor Binding with [123I]S(-)iodobenzamide ([123I]IBZM) in Rat and Human Brain. Nucl. Bed. Biol. 1991, 18, 837–846.
Joyce, J. N.; Janowsky, A.; Neve, K.A. Characterization and Distribution of [125I]Epidepride Binding to Dopamine D2 Receptors in Basal Ganglia and Cortex of Human Brain. J. Pharmacol. Exp. Ther. 1991, 257, 1253–1263.
Innis, R.B.; Malison, R.T.; Al-Tikriti, M.; Hoffer, P.B.; Sybirska, E.H.; Seibyl, J.P.; Zoghbi, S.S.; Baldwin, R.M.; Laruelle, M.; Smith, E.O.; Charney, D.S.; Heninger, G.; Elsworth, J.D.; Roth, R.H. Amphetamine-Stimulated Dopamine Release Competes In Vivo for [123I]ibzM Binding to the D2 Receptor in Nonhuman Primates. Synapse 1992, 10, 177–184.
Hall, H.; Hogberg, T; Halldin, C; Kohler, C; Strom, P.; Ross, S.B.; Larsson, S.A.; Farde, L. NCQ 298, A New Selective iodinated Salicylamide Ligand for the Labelling of Dopamine-D2 Receptors. Psychopharm. 1991, 103,6.
Votaw, J.R.; Kessler, R.M de Paulis, T.; Ansari, M.S.; Mason, N.S.; Schmidt, D.E., Manning, R.G.; Holburn, G..; Quantification of Striatal and Extra-Striatal Dopamine D2 Receptors Using N-Allyl Fluoropropylepidepride. J. Nucl. Med. 1993, 34, 132 (abst.).
Baldwin, R.M.; Al-Tikriti, M.S.; Zea-Ponce, Y.; Zoghbi, S.S.; Sybirska, E.H.; Malison, R.T.; Laruelle, M.; Kung, H.F.; Kessler, R.M de Paulis, T.; Nakatsuka, I.; Saji, H.; Smith, E.O.; Wisniewski, G.; Charney, D.S.; Hoffer, P.B.; Innis, R.B..; In Vivo Comparison of 3 Radioiodinated High Affinity Dopamine D2 Receptor Ligands: IBF, EPID, and 2′-ISP. J. Nucl. Med. 1992, 33, 848 (abst.).
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Manning, R.G., Mason, N.S., de Paulis, T., Kessler, R.M. (1995). Halogenated Benzamides as Ligands for Cerebral Dopamine Receptors. In: Emran, A.M. (eds) Chemists’ Views of Imaging Centers. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-9670-4_28
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DOI: https://doi.org/10.1007/978-1-4757-9670-4_28
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