Competition between 11C-raclopride and endogenous dopamine in Parkinson's disease

ObjectiveThe aim of this study was to understand whether the increase in 11C-raclopride binding in the striatum of patients with Parkinson's disease (PD) is associated with the depletion of endogenous dopamine. MethodsPositron emission tomography (PET) scans of the two dopamine D2 receptor ligands, 11C-raclopride and 11C-N-methylspiperone (11C-NMSP), and the dopamine transporter ligand, 11C-2&bgr;-carbomethoxy-3&bgr;-(4-fluorophenyl)-tropane, were performed on five patients with PD and seven controls. The binding of each tracer was calculated by using a (region–cerebellum)/cerebellum ratio in the caudate, anterior putamen, and posterior putamen. ResultsIn patients with PD, the 11C-raclopride to 11C-NMSP ratios in the posterior putamen, which was the subregion of the striatum with the lowest binding of 11C-2&bgr;-carbomethoxy-3&bgr;-(4-fluorophenyl)-tropane, were the largest among all three subregions of the striatum. In controls, the 11C-raclopride to 11C-NMSP ratios in all three subregions of the striatum were within a constant range. ConclusionIn patients with PD, the kinetic difference between 11C-raclopride and 11C-NMSP was found prominently in the posterior putamen, in which presynaptic degeneration occurred most profoundly. Therefore, we concluded that the increase in 11C-raclopride binding in the striatum of patients with PD was strongly associated with the depletion of endogenous dopamine. 11C-NMSP can be chosen in the place of 11C-raclopride in cases in which it may be essential to eliminate the influence of endogenous dopamine.

[1]  Houeto Jean-Luc.  [Parkinson's disease]. , 2022, La Revue du praticien.

[2]  P. Seeman,et al.  Endogenous dopamine lowers the dopamine D2 receptor density as measured by [3H]raclopride: Implications for positron emission tomography of the human brain , 1989, Synapse.

[3]  S O Ogren,et al.  Specific in vitro and in vivo binding of 3H-raclopride. A potent substituted benzamide drug with high affinity for dopamine D-2 receptors in the rat brain. , 1985, Biochemical pharmacology.

[4]  P. Seeman,et al.  Elevation of dopamine D2 receptors in schizophrenia is underestimated by radioactive raclopride. , 1990, Archives of general psychiatry.

[5]  Juha O Rinne,et al.  Progression of dopaminergic hypofunction in striatal subregions in Parkinson's disease using [18F]CFT PET , 2003, Synapse.

[6]  L. Farde,et al.  Human dopamine receptor subtypes—in vitro binding analysis using3H-SCH 23390 and3H-raclopride , 2005, Journal of Neural Transmission.

[7]  M. Terai,et al.  Comparison of [3H]YM-09151-2 with [3H]spiperone and [3H]raclopride for dopamine d-2 receptor binding to rat striatum. , 1989, European journal of pharmacology.

[8]  M. Mishina,et al.  Presynaptic and postsynaptic nigrostriatal dopaminergic functions in multiple system atrophy , 2008, Neuroreport.

[9]  K. Oda,et al.  Age-related changes of the [11C]CFT binding to the striatal dopamine transporters in the fischer 344 rats: a PET study , 2003, Annals of nuclear medicine.

[10]  C. Halldin,et al.  Comparison of the In Vitro Receptor Binding Properties of N‐[3H]Methylspiperone and [3H]Raclopride to Rat and Human Brain Membranes , 1990, Journal of neurochemistry.

[11]  R S Frackowiak,et al.  Asymmetrical pre-synaptic and post-synpatic changes in the striatal dopamine projection in dopa naïve parkinsonism. Diagnostic implications of the D2 receptor status. , 1993, Brain : a journal of neurology.

[12]  J S Fowler,et al.  Striatal binding of the PET ligand 11C‐raclopride is altered by drugs that modify synaptic dopamine levels , 1993, Synapse.

[13]  K. Oda,et al.  Cerebrospinal fluid metabolite and nigrostriatal dopaminergic function in Parkinson’s disease , 2009, Acta neurologica Scandinavica.

[14]  M. Buyse,et al.  Reproducibility of monoamine metabolite measurements in human cerebrospinal fluid , 1990, Acta neurologica Scandinavica.

[15]  V Kaasinen,et al.  Upregulation of putaminal dopamine D2 receptors in early Parkinson's disease: a comparative PET study with [11C] raclopride and [11C]N-methylspiperone. , 2000, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[16]  B. Långstrom,et al.  Difference in in vivo receptor binding between [3 H]N-methylspiperone and [3 H]raclopride in reserpine-treated mouse brain , 2005, Journal of Neural Transmission / General Section JNT.

[17]  W. Gibb,et al.  Anatomy, pigmentation, ventral and dorsal subpopulations of the substantia nigra, and differential cell death in Parkinson's disease. , 1991, Journal of neurology, neurosurgery, and psychiatry.

[18]  J O Rinne,et al.  Usefulness of a dopamine transporter PET ligand [18F]β-CFT in assessing disability in Parkinson's disease , 1999, Journal of neurology, neurosurgery, and psychiatry.

[19]  S H Snyder,et al.  Positron emission tomographic imaging of the dopamine transporter with 11C‐WIN 35,428 reveals marked declines in mild Parkinson's disease , 1993, Annals of neurology.

[20]  D J Brooks,et al.  An [18F]dopa-PET and clinical study of the rate of progression in Parkinson's disease. , 1996, Brain : a journal of neurology.

[21]  S. Stone-Elander,et al.  Stereoselective binding of 11C-raclopride in living human brain — a search for extrastriatal central D2-dopamine receptors by PET , 2004, Psychopharmacology.

[22]  M. Folstein,et al.  EFFECTS OF AGE ON DOPAMINE AND SEROTONIN RECEPTORS MEASURED BY POSITRON TOMOGRAPHY IN THE LIVING HUMAN BRAIN , 1984, Science.

[23]  Ralph Myers,et al.  Assessment of Spatial Normalization of PET Ligand Images Using Ligand-Specific Templates , 1999, NeuroImage.

[24]  P. Hartvig,et al.  Dopamine receptor properties in Parkinson's disease and Huntington's chorea evaluated by positron emission tomography using 11C‐N‐methyl‐spiperone , 1987, Acta neurologica Scandinavica.

[25]  B Bioulac,et al.  Relationship between the Appearance of Symptoms and the Level of Nigrostriatal Degeneration in a Progressive 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Lesioned Macaque Model of Parkinson's Disease , 2001, The Journal of Neuroscience.

[26]  O. Dalesio,et al.  CSF levels of neurotransmitters in Alzheimer‐type dementia. Effects of ergoloid mesylate , 1985, Acta neurologica Scandinavica.

[27]  Y Agid,et al.  [3H]spiperone binding, dopamine and HVA concentrations in Parkinson's disease and supranuclear palsy. , 1984, European journal of pharmacology.

[28]  D. Wong,et al.  Effects of endogenous dopamine on kinetics of [3H]N‐methylspiperone and [3H]raclopride binding in the rat brain , 1991, Synapse.

[29]  Philip Seeman,et al.  Dopamine D2 receptor density remains constant in treated Parkinson's disease , 1986, Annals of neurology.

[30]  S. Kish,et al.  Uneven pattern of dopamine loss in the striatum of patients with idiopathic Parkinson's disease. Pathophysiologic and clinical implications. , 1988, The New England journal of medicine.

[31]  寺井 道夫.  Comparison of [[3]H]YM-09151-2 with [[3]H]spiperone and [[3]H]raclopride for dopamine D-2 receptor binding to rat striatum , 1994 .

[32]  M. Senda,et al.  Comparison of three PET dopamine D2-like receptor ligands, [11C]raclopride, [11C]nemonapride and [11C]N-methylspiperone, in rats , 1999, Annals of nuclear medicine.

[33]  Christer Halldin,et al.  Precursor synthesis and radiolabelling of the dopamine D2 receptor ligand (11C)raclopride from (11C)methyl triflate , 1999 .

[34]  Manuel Desco,et al.  Influence of the normalization template on the outcome of statistical parametric mapping of PET scans , 2003, NeuroImage.

[35]  C D Marsden,et al.  Differing patterns of striatal 18F‐dopa uptake in Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy , 1990, Annals of neurology.

[36]  A. Antonini,et al.  [11C]raclopride and positron emission tomography in previously untreated patients with Parkinson's disease , 1994, Neurology.

[37]  A. Lees,et al.  Ageing and Parkinson's disease: substantia nigra regional selectivity. , 1991, Brain : a journal of neurology.

[38]  K. Ishii,et al.  Regional analysis of age‐related decline in dopamine transporters and dopamine D2‐like receptors in human striatum , 2009, Synapse.

[39]  F Crivello,et al.  Positron Emission Tomography of the Human Brain , 1999 .

[40]  N. Volkow,et al.  Parallel loss of presynaptic and postsynaptic dopamine markers in normal aging , 1998, Annals of neurology.

[41]  K. Leenders,et al.  Effect of age on D2 dopamine receptors in normal human brain measured by positron emission tomography and 11C-raclopride. , 1993, Archives of neurology.

[42]  J. Korf,et al.  Tracing of dopamine receptors in hemiparkinsonism with positron emission tomography (PET) , 1987, Journal of the Neurological Sciences.

[43]  U Ruotsalainen,et al.  PET study on striatal dopamine D2 receptor changes during the progression of early parkinson's disease , 1993, Movement disorders : official journal of the Movement Disorder Society.