[11C]PE2I: a highly selective radioligand for PET examination of the dopamine transporter in monkey and human brain
Abstract The aim of this study was to explore the potential of a new selective dopamine transporter (DAT) compound as a radioligand for positron emission tomography (PET) examination of DAT in the human brain. The high affinity DAT compound N-(3-iodoprop-2E-enyl)-2β-carbomethoxy-3β-(4-methylphenyl)n...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Halldin, Christer [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2003 |
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| Schlagwörter: |
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| Anmerkung: |
© Springer-Verlag 2003 |
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| Übergeordnetes Werk: |
Enthalten in: European journal of nuclear medicine and molecular imaging - Heidelberg [u.a.] : Springer-Verl., 2002, 30(2003), 9 vom: 13. Juni, Seite 1220-1230 |
|---|---|
| Übergeordnetes Werk: |
volume:30 ; year:2003 ; number:9 ; day:13 ; month:06 ; pages:1220-1230 |
| Links: |
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| DOI / URN: |
10.1007/s00259-003-1212-3 |
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| Katalog-ID: |
SPR003113426 |
|---|
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| 100 | 1 | |a Halldin, Christer |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a [11C]PE2I: a highly selective radioligand for PET examination of the dopamine transporter in monkey and human brain |
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| 520 | |a Abstract The aim of this study was to explore the potential of a new selective dopamine transporter (DAT) compound as a radioligand for positron emission tomography (PET) examination of DAT in the human brain. The high affinity DAT compound N-(3-iodoprop-2E-enyl)-2β-carbomethoxy-3β-(4-methylphenyl)nortropane (PE2I) was radiolabelled by the O-methylation approach and the binding was characterised by PET in cynomolgus monkeys and a healthy man. Metabolite levels in plasma were measured by gradient high-performance liquid chromatography. O-methylation of the corresponding free acid precursor with [11C]methyl triflate gave high radiochemical yield (80%) and specific radioactivity (55 GBq/μmol). [11C]PE2I binding in cynomolgus monkeys was nine times higher in the striatum than in the cerebellum at peak equilibrium, which appeared 55–65 min after injection. Displacement and pretreatment measurements using unlabelled β-CIT, GBR 12909, cocaine, citalopram and maprotiline confirmed that [11C]PE2I binds selectively to DAT. In a preliminary study in one human subject the radioactivity ratios of the striatum and substantia nigra to the cerebellum were 10 and 1.8, respectively, at peak equilibrium, which appeared at 40–50 min and 20 min, respectively, after injection. The fraction of the total radioactivity in monkey and human plasma representing unchanged [11C]PE2I was 15–20% at 40 min after injection. The present characterisation of binding in monkey and man suggests that [11C]PE2I is a suitable PET radioligand for quantitative regional examination of DAT in man. | ||
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| 650 | 4 | |a Dopamine transporter |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Striatum |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Substantia nigra |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a PE2I |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a PET |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Erixon-Lindroth, Nina |4 aut | |
| 700 | 1 | |a Pauli, Stefan |4 aut | |
| 700 | 1 | |a Chou, Yuan-Hwa |4 aut | |
| 700 | 1 | |a Okubo, Yoshiro |4 aut | |
| 700 | 1 | |a Karlsson, Per |4 aut | |
| 700 | 1 | |a Lundkvist, Camilla |4 aut | |
| 700 | 1 | |a Olsson, Hans |4 aut | |
| 700 | 1 | |a Guilloteau, Denis |4 aut | |
| 700 | 1 | |a Emond, Patrick |4 aut | |
| 700 | 1 | |a Farde, Lars |4 aut | |
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10.1007/s00259-003-1212-3 doi (DE-627)SPR003113426 (SPR)s00259-003-1212-3-e DE-627 ger DE-627 rakwb eng Halldin, Christer verfasserin aut [11C]PE2I: a highly selective radioligand for PET examination of the dopamine transporter in monkey and human brain 2003 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag 2003 Abstract The aim of this study was to explore the potential of a new selective dopamine transporter (DAT) compound as a radioligand for positron emission tomography (PET) examination of DAT in the human brain. The high affinity DAT compound N-(3-iodoprop-2E-enyl)-2β-carbomethoxy-3β-(4-methylphenyl)nortropane (PE2I) was radiolabelled by the O-methylation approach and the binding was characterised by PET in cynomolgus monkeys and a healthy man. Metabolite levels in plasma were measured by gradient high-performance liquid chromatography. O-methylation of the corresponding free acid precursor with [11C]methyl triflate gave high radiochemical yield (80%) and specific radioactivity (55 GBq/μmol). [11C]PE2I binding in cynomolgus monkeys was nine times higher in the striatum than in the cerebellum at peak equilibrium, which appeared 55–65 min after injection. Displacement and pretreatment measurements using unlabelled β-CIT, GBR 12909, cocaine, citalopram and maprotiline confirmed that [11C]PE2I binds selectively to DAT. In a preliminary study in one human subject the radioactivity ratios of the striatum and substantia nigra to the cerebellum were 10 and 1.8, respectively, at peak equilibrium, which appeared at 40–50 min and 20 min, respectively, after injection. The fraction of the total radioactivity in monkey and human plasma representing unchanged [11C]PE2I was 15–20% at 40 min after injection. The present characterisation of binding in monkey and man suggests that [11C]PE2I is a suitable PET radioligand for quantitative regional examination of DAT in man. Brain (dpeaa)DE-He213 Dopamine transporter (dpeaa)DE-He213 Striatum (dpeaa)DE-He213 Substantia nigra (dpeaa)DE-He213 PE2I (dpeaa)DE-He213 PET (dpeaa)DE-He213 Erixon-Lindroth, Nina aut Pauli, Stefan aut Chou, Yuan-Hwa aut Okubo, Yoshiro aut Karlsson, Per aut Lundkvist, Camilla aut Olsson, Hans aut Guilloteau, Denis aut Emond, Patrick aut Farde, Lars aut Enthalten in European journal of nuclear medicine and molecular imaging Heidelberg [u.a.] : Springer-Verl., 2002 30(2003), 9 vom: 13. Juni, Seite 1220-1230 (DE-627)359787258 (DE-600)2098375-X 1619-7089 nnns volume:30 year:2003 number:9 day:13 month:06 pages:1220-1230 https://dx.doi.org/10.1007/s00259-003-1212-3 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 30 2003 9 13 06 1220-1230 |
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10.1007/s00259-003-1212-3 doi (DE-627)SPR003113426 (SPR)s00259-003-1212-3-e DE-627 ger DE-627 rakwb eng Halldin, Christer verfasserin aut [11C]PE2I: a highly selective radioligand for PET examination of the dopamine transporter in monkey and human brain 2003 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag 2003 Abstract The aim of this study was to explore the potential of a new selective dopamine transporter (DAT) compound as a radioligand for positron emission tomography (PET) examination of DAT in the human brain. The high affinity DAT compound N-(3-iodoprop-2E-enyl)-2β-carbomethoxy-3β-(4-methylphenyl)nortropane (PE2I) was radiolabelled by the O-methylation approach and the binding was characterised by PET in cynomolgus monkeys and a healthy man. Metabolite levels in plasma were measured by gradient high-performance liquid chromatography. O-methylation of the corresponding free acid precursor with [11C]methyl triflate gave high radiochemical yield (80%) and specific radioactivity (55 GBq/μmol). [11C]PE2I binding in cynomolgus monkeys was nine times higher in the striatum than in the cerebellum at peak equilibrium, which appeared 55–65 min after injection. Displacement and pretreatment measurements using unlabelled β-CIT, GBR 12909, cocaine, citalopram and maprotiline confirmed that [11C]PE2I binds selectively to DAT. In a preliminary study in one human subject the radioactivity ratios of the striatum and substantia nigra to the cerebellum were 10 and 1.8, respectively, at peak equilibrium, which appeared at 40–50 min and 20 min, respectively, after injection. The fraction of the total radioactivity in monkey and human plasma representing unchanged [11C]PE2I was 15–20% at 40 min after injection. The present characterisation of binding in monkey and man suggests that [11C]PE2I is a suitable PET radioligand for quantitative regional examination of DAT in man. Brain (dpeaa)DE-He213 Dopamine transporter (dpeaa)DE-He213 Striatum (dpeaa)DE-He213 Substantia nigra (dpeaa)DE-He213 PE2I (dpeaa)DE-He213 PET (dpeaa)DE-He213 Erixon-Lindroth, Nina aut Pauli, Stefan aut Chou, Yuan-Hwa aut Okubo, Yoshiro aut Karlsson, Per aut Lundkvist, Camilla aut Olsson, Hans aut Guilloteau, Denis aut Emond, Patrick aut Farde, Lars aut Enthalten in European journal of nuclear medicine and molecular imaging Heidelberg [u.a.] : Springer-Verl., 2002 30(2003), 9 vom: 13. Juni, Seite 1220-1230 (DE-627)359787258 (DE-600)2098375-X 1619-7089 nnns volume:30 year:2003 number:9 day:13 month:06 pages:1220-1230 https://dx.doi.org/10.1007/s00259-003-1212-3 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 30 2003 9 13 06 1220-1230 |
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10.1007/s00259-003-1212-3 doi (DE-627)SPR003113426 (SPR)s00259-003-1212-3-e DE-627 ger DE-627 rakwb eng Halldin, Christer verfasserin aut [11C]PE2I: a highly selective radioligand for PET examination of the dopamine transporter in monkey and human brain 2003 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag 2003 Abstract The aim of this study was to explore the potential of a new selective dopamine transporter (DAT) compound as a radioligand for positron emission tomography (PET) examination of DAT in the human brain. The high affinity DAT compound N-(3-iodoprop-2E-enyl)-2β-carbomethoxy-3β-(4-methylphenyl)nortropane (PE2I) was radiolabelled by the O-methylation approach and the binding was characterised by PET in cynomolgus monkeys and a healthy man. Metabolite levels in plasma were measured by gradient high-performance liquid chromatography. O-methylation of the corresponding free acid precursor with [11C]methyl triflate gave high radiochemical yield (80%) and specific radioactivity (55 GBq/μmol). [11C]PE2I binding in cynomolgus monkeys was nine times higher in the striatum than in the cerebellum at peak equilibrium, which appeared 55–65 min after injection. Displacement and pretreatment measurements using unlabelled β-CIT, GBR 12909, cocaine, citalopram and maprotiline confirmed that [11C]PE2I binds selectively to DAT. In a preliminary study in one human subject the radioactivity ratios of the striatum and substantia nigra to the cerebellum were 10 and 1.8, respectively, at peak equilibrium, which appeared at 40–50 min and 20 min, respectively, after injection. The fraction of the total radioactivity in monkey and human plasma representing unchanged [11C]PE2I was 15–20% at 40 min after injection. The present characterisation of binding in monkey and man suggests that [11C]PE2I is a suitable PET radioligand for quantitative regional examination of DAT in man. Brain (dpeaa)DE-He213 Dopamine transporter (dpeaa)DE-He213 Striatum (dpeaa)DE-He213 Substantia nigra (dpeaa)DE-He213 PE2I (dpeaa)DE-He213 PET (dpeaa)DE-He213 Erixon-Lindroth, Nina aut Pauli, Stefan aut Chou, Yuan-Hwa aut Okubo, Yoshiro aut Karlsson, Per aut Lundkvist, Camilla aut Olsson, Hans aut Guilloteau, Denis aut Emond, Patrick aut Farde, Lars aut Enthalten in European journal of nuclear medicine and molecular imaging Heidelberg [u.a.] : Springer-Verl., 2002 30(2003), 9 vom: 13. Juni, Seite 1220-1230 (DE-627)359787258 (DE-600)2098375-X 1619-7089 nnns volume:30 year:2003 number:9 day:13 month:06 pages:1220-1230 https://dx.doi.org/10.1007/s00259-003-1212-3 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 30 2003 9 13 06 1220-1230 |
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10.1007/s00259-003-1212-3 doi (DE-627)SPR003113426 (SPR)s00259-003-1212-3-e DE-627 ger DE-627 rakwb eng Halldin, Christer verfasserin aut [11C]PE2I: a highly selective radioligand for PET examination of the dopamine transporter in monkey and human brain 2003 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag 2003 Abstract The aim of this study was to explore the potential of a new selective dopamine transporter (DAT) compound as a radioligand for positron emission tomography (PET) examination of DAT in the human brain. The high affinity DAT compound N-(3-iodoprop-2E-enyl)-2β-carbomethoxy-3β-(4-methylphenyl)nortropane (PE2I) was radiolabelled by the O-methylation approach and the binding was characterised by PET in cynomolgus monkeys and a healthy man. Metabolite levels in plasma were measured by gradient high-performance liquid chromatography. O-methylation of the corresponding free acid precursor with [11C]methyl triflate gave high radiochemical yield (80%) and specific radioactivity (55 GBq/μmol). [11C]PE2I binding in cynomolgus monkeys was nine times higher in the striatum than in the cerebellum at peak equilibrium, which appeared 55–65 min after injection. Displacement and pretreatment measurements using unlabelled β-CIT, GBR 12909, cocaine, citalopram and maprotiline confirmed that [11C]PE2I binds selectively to DAT. In a preliminary study in one human subject the radioactivity ratios of the striatum and substantia nigra to the cerebellum were 10 and 1.8, respectively, at peak equilibrium, which appeared at 40–50 min and 20 min, respectively, after injection. The fraction of the total radioactivity in monkey and human plasma representing unchanged [11C]PE2I was 15–20% at 40 min after injection. The present characterisation of binding in monkey and man suggests that [11C]PE2I is a suitable PET radioligand for quantitative regional examination of DAT in man. Brain (dpeaa)DE-He213 Dopamine transporter (dpeaa)DE-He213 Striatum (dpeaa)DE-He213 Substantia nigra (dpeaa)DE-He213 PE2I (dpeaa)DE-He213 PET (dpeaa)DE-He213 Erixon-Lindroth, Nina aut Pauli, Stefan aut Chou, Yuan-Hwa aut Okubo, Yoshiro aut Karlsson, Per aut Lundkvist, Camilla aut Olsson, Hans aut Guilloteau, Denis aut Emond, Patrick aut Farde, Lars aut Enthalten in European journal of nuclear medicine and molecular imaging Heidelberg [u.a.] : Springer-Verl., 2002 30(2003), 9 vom: 13. Juni, Seite 1220-1230 (DE-627)359787258 (DE-600)2098375-X 1619-7089 nnns volume:30 year:2003 number:9 day:13 month:06 pages:1220-1230 https://dx.doi.org/10.1007/s00259-003-1212-3 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 30 2003 9 13 06 1220-1230 |
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10.1007/s00259-003-1212-3 doi (DE-627)SPR003113426 (SPR)s00259-003-1212-3-e DE-627 ger DE-627 rakwb eng Halldin, Christer verfasserin aut [11C]PE2I: a highly selective radioligand for PET examination of the dopamine transporter in monkey and human brain 2003 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag 2003 Abstract The aim of this study was to explore the potential of a new selective dopamine transporter (DAT) compound as a radioligand for positron emission tomography (PET) examination of DAT in the human brain. The high affinity DAT compound N-(3-iodoprop-2E-enyl)-2β-carbomethoxy-3β-(4-methylphenyl)nortropane (PE2I) was radiolabelled by the O-methylation approach and the binding was characterised by PET in cynomolgus monkeys and a healthy man. Metabolite levels in plasma were measured by gradient high-performance liquid chromatography. O-methylation of the corresponding free acid precursor with [11C]methyl triflate gave high radiochemical yield (80%) and specific radioactivity (55 GBq/μmol). [11C]PE2I binding in cynomolgus monkeys was nine times higher in the striatum than in the cerebellum at peak equilibrium, which appeared 55–65 min after injection. Displacement and pretreatment measurements using unlabelled β-CIT, GBR 12909, cocaine, citalopram and maprotiline confirmed that [11C]PE2I binds selectively to DAT. In a preliminary study in one human subject the radioactivity ratios of the striatum and substantia nigra to the cerebellum were 10 and 1.8, respectively, at peak equilibrium, which appeared at 40–50 min and 20 min, respectively, after injection. The fraction of the total radioactivity in monkey and human plasma representing unchanged [11C]PE2I was 15–20% at 40 min after injection. The present characterisation of binding in monkey and man suggests that [11C]PE2I is a suitable PET radioligand for quantitative regional examination of DAT in man. Brain (dpeaa)DE-He213 Dopamine transporter (dpeaa)DE-He213 Striatum (dpeaa)DE-He213 Substantia nigra (dpeaa)DE-He213 PE2I (dpeaa)DE-He213 PET (dpeaa)DE-He213 Erixon-Lindroth, Nina aut Pauli, Stefan aut Chou, Yuan-Hwa aut Okubo, Yoshiro aut Karlsson, Per aut Lundkvist, Camilla aut Olsson, Hans aut Guilloteau, Denis aut Emond, Patrick aut Farde, Lars aut Enthalten in European journal of nuclear medicine and molecular imaging Heidelberg [u.a.] : Springer-Verl., 2002 30(2003), 9 vom: 13. Juni, Seite 1220-1230 (DE-627)359787258 (DE-600)2098375-X 1619-7089 nnns volume:30 year:2003 number:9 day:13 month:06 pages:1220-1230 https://dx.doi.org/10.1007/s00259-003-1212-3 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 30 2003 9 13 06 1220-1230 |
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English |
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Enthalten in European journal of nuclear medicine and molecular imaging 30(2003), 9 vom: 13. Juni, Seite 1220-1230 volume:30 year:2003 number:9 day:13 month:06 pages:1220-1230 |
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Enthalten in European journal of nuclear medicine and molecular imaging 30(2003), 9 vom: 13. Juni, Seite 1220-1230 volume:30 year:2003 number:9 day:13 month:06 pages:1220-1230 |
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Brain Dopamine transporter Striatum Substantia nigra PE2I PET |
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European journal of nuclear medicine and molecular imaging |
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Halldin, Christer @@aut@@ Erixon-Lindroth, Nina @@aut@@ Pauli, Stefan @@aut@@ Chou, Yuan-Hwa @@aut@@ Okubo, Yoshiro @@aut@@ Karlsson, Per @@aut@@ Lundkvist, Camilla @@aut@@ Olsson, Hans @@aut@@ Guilloteau, Denis @@aut@@ Emond, Patrick @@aut@@ Farde, Lars @@aut@@ |
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The high affinity DAT compound N-(3-iodoprop-2E-enyl)-2β-carbomethoxy-3β-(4-methylphenyl)nortropane (PE2I) was radiolabelled by the O-methylation approach and the binding was characterised by PET in cynomolgus monkeys and a healthy man. Metabolite levels in plasma were measured by gradient high-performance liquid chromatography. O-methylation of the corresponding free acid precursor with [11C]methyl triflate gave high radiochemical yield (80%) and specific radioactivity (55 GBq/μmol). [11C]PE2I binding in cynomolgus monkeys was nine times higher in the striatum than in the cerebellum at peak equilibrium, which appeared 55–65 min after injection. Displacement and pretreatment measurements using unlabelled β-CIT, GBR 12909, cocaine, citalopram and maprotiline confirmed that [11C]PE2I binds selectively to DAT. 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Halldin, Christer |
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Halldin, Christer misc Brain misc Dopamine transporter misc Striatum misc Substantia nigra misc PE2I misc PET [11C]PE2I: a highly selective radioligand for PET examination of the dopamine transporter in monkey and human brain |
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[11C]PE2I: a highly selective radioligand for PET examination of the dopamine transporter in monkey and human brain Brain (dpeaa)DE-He213 Dopamine transporter (dpeaa)DE-He213 Striatum (dpeaa)DE-He213 Substantia nigra (dpeaa)DE-He213 PE2I (dpeaa)DE-He213 PET (dpeaa)DE-He213 |
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Halldin, Christer Erixon-Lindroth, Nina Pauli, Stefan Chou, Yuan-Hwa Okubo, Yoshiro Karlsson, Per Lundkvist, Camilla Olsson, Hans Guilloteau, Denis Emond, Patrick Farde, Lars |
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Elektronische Aufsätze |
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Halldin, Christer |
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10.1007/s00259-003-1212-3 |
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[11c]pe2i: a highly selective radioligand for pet examination of the dopamine transporter in monkey and human brain |
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[11C]PE2I: a highly selective radioligand for PET examination of the dopamine transporter in monkey and human brain |
| abstract |
Abstract The aim of this study was to explore the potential of a new selective dopamine transporter (DAT) compound as a radioligand for positron emission tomography (PET) examination of DAT in the human brain. The high affinity DAT compound N-(3-iodoprop-2E-enyl)-2β-carbomethoxy-3β-(4-methylphenyl)nortropane (PE2I) was radiolabelled by the O-methylation approach and the binding was characterised by PET in cynomolgus monkeys and a healthy man. Metabolite levels in plasma were measured by gradient high-performance liquid chromatography. O-methylation of the corresponding free acid precursor with [11C]methyl triflate gave high radiochemical yield (80%) and specific radioactivity (55 GBq/μmol). [11C]PE2I binding in cynomolgus monkeys was nine times higher in the striatum than in the cerebellum at peak equilibrium, which appeared 55–65 min after injection. Displacement and pretreatment measurements using unlabelled β-CIT, GBR 12909, cocaine, citalopram and maprotiline confirmed that [11C]PE2I binds selectively to DAT. In a preliminary study in one human subject the radioactivity ratios of the striatum and substantia nigra to the cerebellum were 10 and 1.8, respectively, at peak equilibrium, which appeared at 40–50 min and 20 min, respectively, after injection. The fraction of the total radioactivity in monkey and human plasma representing unchanged [11C]PE2I was 15–20% at 40 min after injection. The present characterisation of binding in monkey and man suggests that [11C]PE2I is a suitable PET radioligand for quantitative regional examination of DAT in man. © Springer-Verlag 2003 |
| abstractGer |
Abstract The aim of this study was to explore the potential of a new selective dopamine transporter (DAT) compound as a radioligand for positron emission tomography (PET) examination of DAT in the human brain. The high affinity DAT compound N-(3-iodoprop-2E-enyl)-2β-carbomethoxy-3β-(4-methylphenyl)nortropane (PE2I) was radiolabelled by the O-methylation approach and the binding was characterised by PET in cynomolgus monkeys and a healthy man. Metabolite levels in plasma were measured by gradient high-performance liquid chromatography. O-methylation of the corresponding free acid precursor with [11C]methyl triflate gave high radiochemical yield (80%) and specific radioactivity (55 GBq/μmol). [11C]PE2I binding in cynomolgus monkeys was nine times higher in the striatum than in the cerebellum at peak equilibrium, which appeared 55–65 min after injection. Displacement and pretreatment measurements using unlabelled β-CIT, GBR 12909, cocaine, citalopram and maprotiline confirmed that [11C]PE2I binds selectively to DAT. In a preliminary study in one human subject the radioactivity ratios of the striatum and substantia nigra to the cerebellum were 10 and 1.8, respectively, at peak equilibrium, which appeared at 40–50 min and 20 min, respectively, after injection. The fraction of the total radioactivity in monkey and human plasma representing unchanged [11C]PE2I was 15–20% at 40 min after injection. The present characterisation of binding in monkey and man suggests that [11C]PE2I is a suitable PET radioligand for quantitative regional examination of DAT in man. © Springer-Verlag 2003 |
| abstract_unstemmed |
Abstract The aim of this study was to explore the potential of a new selective dopamine transporter (DAT) compound as a radioligand for positron emission tomography (PET) examination of DAT in the human brain. The high affinity DAT compound N-(3-iodoprop-2E-enyl)-2β-carbomethoxy-3β-(4-methylphenyl)nortropane (PE2I) was radiolabelled by the O-methylation approach and the binding was characterised by PET in cynomolgus monkeys and a healthy man. Metabolite levels in plasma were measured by gradient high-performance liquid chromatography. O-methylation of the corresponding free acid precursor with [11C]methyl triflate gave high radiochemical yield (80%) and specific radioactivity (55 GBq/μmol). [11C]PE2I binding in cynomolgus monkeys was nine times higher in the striatum than in the cerebellum at peak equilibrium, which appeared 55–65 min after injection. Displacement and pretreatment measurements using unlabelled β-CIT, GBR 12909, cocaine, citalopram and maprotiline confirmed that [11C]PE2I binds selectively to DAT. In a preliminary study in one human subject the radioactivity ratios of the striatum and substantia nigra to the cerebellum were 10 and 1.8, respectively, at peak equilibrium, which appeared at 40–50 min and 20 min, respectively, after injection. The fraction of the total radioactivity in monkey and human plasma representing unchanged [11C]PE2I was 15–20% at 40 min after injection. The present characterisation of binding in monkey and man suggests that [11C]PE2I is a suitable PET radioligand for quantitative regional examination of DAT in man. © Springer-Verlag 2003 |
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[11C]PE2I: a highly selective radioligand for PET examination of the dopamine transporter in monkey and human brain |
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| score |
7.402916 |