Zur klinischen Wertigkeit der zerebralen Dopamin-D₂-Rezeptorszintigraphie

Zusammenfassung

Die vorliegende Arbeit gibt eine Übersicht über Befunde und klinische Indikationen zur Dopamin-D₂-Rezeptorszintigraphie. Methoden zur Untersuchung der D₂-Rezeptoren sind die Positronen-Emissions-Tomographie (PET) mit ¹¹C- oder ¹⁸F-markierten Butyrophenonen oder Benza- miden oder die Einzelphotonen-Emissions-Tomographie (SPECT) mit ¹²³l-lodobenzamid (IBZM). Die wichtigste neurologische Indikation ist die Differentialdiagnose des Parkinsonismus: In frühen Stadien des Morbus Parkinson findet sich eine Erhöhung der Striatalen D₂-Rezeptorbin- dung (D₂-RB) im Vergleich zu gesunden Normalpersonen. Patienten mit einem Steele-Richardson-Olszewski-Syndrom oder einer Multisystem- atrophie hingegen, die therapeutisch schwierig einzustellen sind, zeigen eine Verringerung der striatalen D₂-RB. Das ebenfalls abzugrenzende medikamentös induzierte Parkinson-Syndrom beruht auf einer Blockade der D₂-Rezeptoren, die durch die Dopamin-D₂-Rezeptorszintigraphie nachgewiesen werden kann. Weitere mögliche Indikationen bestehen in der Psychiatrie: Bei schizophrenen Patienten, die mit Neuroleptika behandelt werden, ist die Bestimmung der »Receptor Occupancy« sinnvoll, um die optimale Medikamentendosis zu bestimmen. Außerdem ermöglicht die D₂-Rezeptorszintigraphie bei diesen Patienten die Differentialdiagnose zwischen dem malignen Neuroleptikasyndrom und der febrilen Katatonie. Bei Suchterkrankungen könnte die Methode möglicherweise zur Prädiktion und Verlaufskontrolle neurochemischer Veränderungen im Rahmen einer Entwöhnungsbehandlung genutzt werden. Bei der Depression schließlich kann die Bestimmung der D₂-RB die Wahl der Therapie für den Kliniker vereinfachen: Neue klinische Befunde deuten an, daß Patienten mit niedriger D₂-RB gut auf eine medikamentöse Therapie ansprechen, während bei Patienten mit hoher D₂-RB u.a. eine Schlafentzugsbehandlung aussichtsreich ist.

Summary

The present review describes findings and clinical indications for the dopamine D₂ receptor scintigraphy. Methods for the examination of D₂ receptors are positron emission tomography (PET) using ¹¹C- or ¹⁸F-labelled butyrophenones or benzamides or single photon emission tomography (SPECT) using ¹²³l-iodobenzamide (IBZM) respectively. The most important indication in neurology is the differential diagnosis of Parkinsonism: patients with early Parkinson’s disease show an increased D₂ receptor binding (D₂-RB) compared to control subjects. However, patients suffering from Steele-Richardson-Olszewski-Syndrome or Multiple System Atrophy show a decreased D₂-RB and are generally non-responsive to treatment. Postsynaptic blockade of D₂ receptors results in a drug induced Parkinsonian syndrome, which can be diagnosed by D₂ scintigraphy. Further possible indications occur in psychiatry: the assessment of receptor occupancy is useful in schizophrenic patients treated with neuroleptics. Additionally, D₂ receptor scintigraphy might help to clarify the differential diagnosis between neuroleptic malignant syndrome and lethal catatonia. The method might be useful for supervising neurobio- chemical changes in drug dependency and during withdrawal. Assessment of dopamine D₂ receptor binding can simplify the choice of therapy in depressive disorder: patients showing a low D₂ binding are likely to improve following an antidepressive drug treatment whereas sleep deprivation is promising in patients with high D₂ binding.

Schlüsselwörter

Dopamin - Neurologie - Psychiatrie - Dopamin-D₂-Rezeptoren - PET - SPECT

Keywords

Dopamine - neurology - psychiatry - dopamine D₂ receptor - PET - SPECT - Review

• Literatur

• 1 Antonini A, Schwarz J, Oertel WH. et al. [11C]raclopride and positron emission tomography in previously untreated patients with Parkinson’s disease: Influence of L-dopa and lisuride therapy on striatal dopamine D2-receptors. Neurology 1994; 44: 1325-9.
• 2 Antonini A, Vontobel P, Psylla M. et al. Complementary positron emission tomographic studies of the striatal dopaminergic system in Parkinson’s disease. Arch Neurol 1995; 52: 1183-90.
• 3 Arnett CD, Shiue CY, Wolf AP. et al. Comparison of three 18F-labeled butyrophenone neuroleptic drugs in the baboon using positron emission tomography. J Neurochem 1985; 44: 835-44.
• 4 Boy C, Klimke A, Holschbach M. et al. Imaging dopamine-D4-receptors in the living primate brain: A positron emission tomography study using the novel Dl-/D4-antagonist [11C]SDZ GLC 756. Synapse. 1998 im Druck.
• 5 Bruecke T, Woeber C, Podreka I. et al. D2 receptor blockade by flunarizine and cinnarizine explains extrapyramidal side effects. A SPECT study. J Cereb Blood Flow Metab 1995; 15: 513-8.
• 6 Buchali K, Flade H, Johannsen B. et al. A preclinical study of the organ distribution and radiation dosage of radioiodinated iodolisuride. Nuklearmedizin 1991; 30: 137-40.
• 7 D’haenen HA, Bossuyt A. Dopamine D2 receptors in depression measured with single photon emission computed tomography. Biol Psychiatry 1994; 35: 128-32.
• 8 Diehl DJ, Gershon S. The role of dopamine in mood disorders. Compr Psychiatry 1992; 33: 115-20.
• 9 Ebert D, Feistel H, Kaschka W. et al. Single photon emission computerized tomography assessment of cerebral dopamine D2 receptor blockade in depression before and after sleep deprivation – preliminary results. Biol Psychiatry 1994; 35: 880-5.
• 10 Ehrin E, Farde L, Depaulis T. et al. Preparation of llC-labelled raclopride, a new potent dopamine receptor antagonist: preliminary PET studies of cerebral dopamine receptors in monkey. Int J Appl Radiat Isot 1985; 36: 269-73.
• 11 Farde L, Ehrin E, Eriksson L. et al. Substituted benzamides as ligands for visualization of dopamine receptor binding in the human brain by positron emission tomography. Proc Natl Acad Sei USA 1985; 82: 3863-7.
• 12 Farde L, Hall H, Ehrin E. et al. Quantitative analysis of D2 dopamine receptor binding in the living human brain by PET. Science 1986; 231: 258-61.
• 13 Farde L, Nordstrom AL. PET analysis indicates atypical central dopamine receptor occupancy in clozapine-treated patients. Br J Psychiatry Suppl. 1992: 30-3.
• 14 Farde L, Wiesel FA, Stone-Elander S. et al. D2 dopamine receptors in neuroleptic-naive schizophrenic patients – a positron emission tomography study with [11C]raclopride. Arch Gen Psychiatry 1990; 47: 213-9.
• 15 Fornaguera J, Huston JP, Carey RJ. Stimulation of Dl- or D2-receptors in drug-naive rats with different degrees of unilateral nigro-striatal dopamine lesions. Psychopharmacology 1995; 119: 145-54.
• 16 Fowler JS, Arnett CD, Wolf AP. et al. 11C- spiroperidol: synthesis, specific activity determination, and biodistribution in mice. J Nucl Med 1982; 23: 437-45.
• 17 Hall H, Sedvall G, Magnusson O. et al. Distribution of Dl- and D2-dopamine receptors, and dopamine and its metabolites in the human brain. Neuropsychopharmacology 1994; 11: 245-56.
• 18 Hierholzer J, Cordes M, Schelosky L. et al. Bestimmung der zerebralen Dopamin-(D2)-Rezeptoren-Dichte mit Hilfe der 123Jod-IB-ZM-SPECT bei Patienten mit Morbus Parkinson. Roefo 1992; 157: 390-8.
• 19 Ichise M, Toyama H, Fornazzari L. et al. Iodine-123-IBZM dopamine D2 receptor and technetium-99m-HMPAO brain perfusion SPECT in the evaluation of patients with and subjects at risk for Huntington’s disease. J Nucl Med 1993; 34: 1274-81.
• 20 Jauss M, Krack P, Franz M. et al. Imaging of dopamine receptors with [123I]iodobenzamide single-photon emission-computed tomography in neuroleptic malignant syndrome. Mov Disord 1996; 11: 726-8.
• 21 Kessler RM, Ansari MS, Schmidt DE. et al. 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 Sei 1991; 49: 617-28.
• 22 Klimke A, Klieser E. Catatonia. Current therapeutic recommendations. CNS Drugs 1994; 2: 280-91.
• 23 Klimke A, Klieser E. Das atypische Neuroleptikum Clozapin (Leponex) – aktueller Kenntnisstand und neuere klinische Aspekte. Fortschr Neurol Psychiatr 1995; 63: 173-93.
• 24 Klimke A, Larisch R, Janz A. et al. Dopamine D2 receptor binding before and after treatment of major depression measured by single photon emission computed tomography. Psychiatry Res Neuroimaging. 1998 im Druck.
• 25 Kuikka JT, Akerman KK, Hiltunen J. et al. Striatal and extrastriatal imaging of dopamine D2 receptors in the living human brain with [123I]epidepride SPET. Eur J Nucl Med 1997; 24: 483-7.
• 26 Kung HF, Pan S, Kung MP. et al. 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.
• 27 Larisch R, Klimke A, Vosberg H. et al. in vivo evidence for the involvement of dopamine-D2 receptors in striatum and anterior cingulate gyrus in major depression. Neuro-Image 1997; 5: 251-60.
• 28 Laulumaa V, Kuikka JT, Soininen H. et al. Imaging of D2 dopamine receptors of patients with Parkinson’s disease using single photon emission computed tomography and iodobenzamide 1123. Arch Neurol 1993; 50: 509-12.
• 29 Lidow MS, Goldman-Rakic PS, Rakic P. et al. Dopamine D2 receptors in the cerebral cortex: distribution and pharmacological characterization with [3H]raclopride. Proc Natl Acad Sei USA 1989; 86: 6412-6.
• 30 Mach RH, Nader MA, Ehrenkaufer RL. et al. Use of positron emission tomography to study the dynamics of psychostimulant-induced dopamine release. Pharmacol Biochem Behav 1997; 57: 477-86.
• 31 Martinot JL, Paillere-Martinot ML, Loc’h C. et al. The estimated density of D2 striatal receptors in schizophrenia. A study with positron emission tomography and 76Br-bromolisuride. Br J Psychiatry 1991; 158: 346-50.
• 32 Mazière B, Loc’h C. Synthesis of radiohalogenated derivates of lisuride. J Label Comp Radiopharm 1989; 26: 100-1.
• 33 Meador-Woodruff JH, Damask JP, Wang J. et al. Dopamine receptor mRNA expression in human striatum and neocortex. Neuropsychopharmacology 1996; 15: 17-29.
• 34 Meador-Woodruff JH, Mansour A, Grandy DK. et al. Distribution of D5 dopamine receptor mRNA in rat brain. Neurosci Lett 1992; 145: 209-12.
• 35 Moerlein SM, Banks WR, Parkinson D. Production of fluorine-18 labeled (3-N-methyl)benperidol for PET investigation of cerebral dopaminergic receptor binding. Int J Radiat Appl Instrum Part A 1992; 43: 913-7.
• 36 Pearlson GD, Tune LE, Wong DF. et al. Quantitative D2 dopamine receptor PET and structural MRI changes in late-onset schizophrenia. Schizophr Bull 1993; 19: 783-95.
• 37 Pilowsky LS, Costa DC, Ell PJ. et al. D2 dopamine receptor binding in the basal ganglia of antipsychotic-free schizophrenic patients. An 123I-IBZM single photon emission computerised tomography study. Br J Psychiatry 1994; 164: 16-26.
• 38 Primus RJ, Thurkauf A, Xu J. et al. II. Localization and characterization of dopamine D4 binding sites in rat and human brain by use of the novel, D4 receptor-selective ligand [3HJNGD 94-1. J Pharmacol Exp Ther 1997; 282: 1020-7.
• 39 Reiche W, Grundmann M, Huber G. Die Dopamin(D2)-Rezeptor-SPECT mit 1231-Jodbenzamid (IBZM) in der Diagnostik des Parkinson-Syndroms. Radiologe 1995; 35: 838-43.
• 40 Rinne JO, Hietala J, Ruotsalainen U. et al. Decrease in human striatal dopamine D2 receptor density with age: a PET study with [11C]raclopride. J Cereb Blood Flow Metab 1993; 13: 310-4.
• 41 Rinne UK, Laihinen A, Rinne JO. et al. Positron emission tomography demonstrates dopamine D2 receptor supersensitivity in the striatum of patients with early Parkinson’s disease. Mov Disord 1990; 5: 55-9.
• 42 Schelosky L, Hierholzer J, Wissel J. et al. Correlation of clinical response in apomorphine test with D2-receptor status as demonstrated by 1231 IBZM-SPECT. Mov Disord 1993; 8: 453-8.
• 43 Schwarz J, Tatsch K, Arnold G. et al. 1231- iodobenzamide-SPECT predicts dopaminergic responsiveness in patients with de novo parkinsonism. Neurology 1992; 42: 556-61.
• 44 Schwarz J, Tatsch K, Arnold G. et al. 1231- iodobenzamide-SPECT in 83 patients with de novo parkinsonism. Neurology 1993; 43 (Suppl. 06) S17-20.
• 45 Sedvall G, Farde L, Persson A. et al. Imaging of neurotransmitter receptors in the living human brain. Arch Gen Psychiatry 1986; 43: 995-1005.
• 46 Seeman P. Schizophrenia as a brain disease. Arch Neurol 1993; 50: 1093-7.
• 47 Seeman P, Corbett R, Nam D. et al. Dopamine and serotonin receptors: amino acid sequences, and clinical role in neuroleptic parkinsonism. Jpn J Pharmacol 1996; 71: 187-204.
• 48 Seeman P, Grigoriadis DE. Dopamine receptors in brain and periphery. Neurochem Int 1987; 10: 1-25.
• 49 Smith M, Wolf AP, Brodie JD. et al. Serial [18F]N-methylspiroperidol PET studies to measure changes in antipsychotic drug D-2 receptor occupancy in schizophrenic patients. Biol Psychiatry 1988; 23: 653-63.
• 50 Suzuki M, Hurd YL, Sokoloff P. et al. D3 dopamine receptor mRNA is widely expressed in the human brain. Brain Res 1998; 779: 58-74.
• 51 Tune LE, Wong DF, Pearlson G. et al. Dopamine D2 receptor density estimates in schizophrenia: a positron emission tomography study with llC-N-methylspiperone. Psychiatry Res 1993; 49: 219-37.
• 52 van Royen E, Verhoeff NP, Speelman JD. et al. Multiple system atrophy and progressive supranuclear palsy. Diminished striatal D2 dopamine receptor activity demonstrated by 123I-IBZM single photon emission computed tomography. Arch Neurol 1993; 50: 513-6.
• 53 Volkow ND, Wang GJ, Fowler JS. et al. Decreased striatal dopaminergic responsiveness in detoxified cocaine-dependent subjects. Nature 1997; 386: 830-3.
• 54 Wagner Jr. HN, Burns HD, Dannais RF. et al. Imaging dopamine receptors in the human brain by positron tomography. Science 1983; 221: 1264-6.
• 55 Wang GJ, Volkow ND, Logan J. et al. Evaluation of age-related changes in serotonin 5-HT2 and dopamine D2 receptor availability in healthy human subjects. Life Sei 1995; 56: PL249-53.
• 56 Willner P, Muscat R, Papp M. et al. Dopamine, depression and anti-depressant drugs. The Mesolimbic Dopamine System: From Motivation to Action.. Willner P, Scheel-Krueger J. Chichester, New York, Brisbane: Wiley & Sons; 387-410.
• 57 Wong DF, Wagner Jr. HN, Pearlson G. Dopamine receptor binding of C-11-3-N- methylspiperone in the caudate in schizophrenia and bipolar disorder: A preliminary report. Psychopharmacol Bull 1985; 21: 595-7.
• 58 Wong DF, Wagner Jr. HN, Tune LE. et al. Positron emission tomography reveals elevated D2 dopamine receptors in drugnaive schizophrenics. Science 1986; 234: 1558-63.