Increased density of dopamine D2 receptors in the putamen, but not in the caudate nucleus in early Parkinson's disease: a PET study with [11C]raclopride

Rinne, Juha O.; Laihinen, A.; Ruottinen, Hanna; Ruotsalainen, Ulla; Någren, Kjell; Lehikoinen, Pertti; Oikonen, Vesa; Rinne, U. K.

doi:10.1016/0022-510x(95)00137-q

Cited by 105 publications

(76 citation statements)

References 28 publications

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“…By analogy with postmortem ligand-binding studies, Farde et al (1986) and Wong et al (1986) and a number of followers, including ourselves (Delforge et al, 1995(Delforge et al, , 1999Holden et al, 2002;Ito et al, 1998), proposed the administration of multiple concentrations of the PET tracer as a means to measure separately density and apparent affinity in vivo. To date, most applications of these multiple ligand concentration receptor assays (MLCRA) remain devoted to the study of receptor parameters in stable systems, that is, in normal subjects or subjects with long term, chronic conditions such as parkinsonism (Rinne et al, 1995;Doudet et al, 2002) or schizophrenia (Farde, 1987). Nevertheless, even in stable systems, the in vivo and in vitro measurements of density and affinity can yield widely different results.…”

Section: Introductionmentioning

confidence: 99%

Sequential versus Nonsequential Measurement of Density and Affinity of Dopamine D2 Receptors with [¹¹C]Raclopride: 2: Effects of DAT Inhibitors

Doudet

Ruth

Holden

2005

J Cereb Blood Flow Metab

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The multiple ligand concentration receptor assays (MLCRA) method allows, in a stable condition, reliable and reproducible measurements of the density and affinity of the dopamine (DA) D 2 receptors with [11 C]raclopride, using either a sequential method (two or more scans in one day) or a nonsequential method (two or more scans over days or weeks). We have shown that measurement of receptor density and affinity is also possible after an acute pharmacological challenge with methamphetamine and that both scanning protocols yield similar values. However, our attempts to measure receptor density and affinity after a pharmacological challenge with another class of drugs that lead to the same outcome, increase in synaptic DA concentrations, revealed opposite results with the two scanning methods: a decrease in receptor density with the sequential method and an increase in affinity with a nonsequential method. These results show the impact of the timedependency of the effects of an 'acute' pharmacological challenge on MLCRA studies. A theoretical simulation is presented to account for the discrepancy in the sequential and nonsequential data. A possible alternate scanning paradigm is proposed to avoid the confounding effect of time variability of the endogenous ligand synaptic concentrations in the sequential condition.

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Section: Introductionmentioning

confidence: 99%

Sequential versus Nonsequential Measurement of Density and Affinity of Dopamine D2 Receptors with [¹¹C]Raclopride: 2: Effects of DAT Inhibitors

Doudet

Ruth

Holden

2005

J Cereb Blood Flow Metab

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“…It had been shown that both B max and BP Ã are elevated in untreated patients with PD and in an animal model of PD compared with control values (Rinne et al, 1995;Doudet et al, 2002;Doudet and Holden, 2003). Therefore, to confirm that the animals in this study had an increased B max and BP Ã for raclopride in the lesioned putamen compared with the contralateral side, as is typical for PD, we used one-tailed paired t-tests.…”

Section: Discussionmentioning

confidence: 57%

“…The animals used in our study exhibited alterations in dopaminergic markers on the lesioned side typical of untreated PD patients and of the MPTP model of PD in animals. These included an increase in BP Ã , elevation in B max , and reduction in amphetamine-induced decrease of [ 11 C]raclopride specific binding (Rinne et al, 1995;PerezOtano et al, 1994;Doudet et al, 2000). In addition, the findings were more pronounced in the putamen than in the caudate nucleus.…”

Section: Discussionmentioning

confidence: 98%

“…However, published results show that the differences between control and PD cases were nearly equal whether measurements were of BP Ã or of B max in vivo (Doudet et al, 2002;Doudet and Holden, 2003;Rinne et al, 1995). These observations suggest that the fraction of receptors available for binding dopamine, and consequently, the fractional occupancy of D2 receptors by dopamine, is not changed in PD.…”

Section: Introductionmentioning

confidence: 96%

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Estimation of D2-like Receptor Occupancy by Dopamine in the Putamen of Hemiparkinsonian Monkeys

Chefer

Kimes

Matochik

et al. 2007

Neuropsychopharmacol

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To advance understanding of the neurochemical changes in Parkinson's disease (PD), we compared D2-like dopamine receptor occupancy by dopamine in the control and lesioned putamen of four pig-tailed macaques treated unilaterally with MPTP. PET and in vitro binding techniques were used to measure binding potential (BP*) and density of D2-like dopamine receptors (B max ), respectively. As would be expected in PD, relatively higher values of BP* and B max and less amphetamine-induced decrease in [11 C]raclopride binding were observed in the lesioned compared with the contralateral putamen in each animal. The percent differences between lesioned and contralateral sides were similar whether the measurements were of [ 11 C]raclopride BP* or B max values, measured in vivo and in vitro, respectively. As [ 11 C]raclopride BP* is a measure of the density of D2-like dopamine receptors available for radioligand binding (i.e., not occupied by dopamine), these findings suggest that the fractional occupancy of receptors by endogenous dopamine in the lesioned putamen is nearly equal to that in the contralateral putamen. Therefore, the absolute number of receptors occupied by dopamine, which is a product of receptor density and fractional occupancy by dopamine, is greater in the lesioned than in the contralateral putamen. One possible explanation for the lack of differences in fractional occupancy of D2 receptors by dopamine (despite a loss in available dopamine) is a lesion-induced increase in a portion of low-affinity D2 receptors to a state of high affinity for dopamine.

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“…This appears to reflect asymmetry in the progression of basal ganglia pathology (Wenning et al 1998;Rinne et al 1995). It has been proposed that antipsychotic EPSE may demonstrate less asymmetry than that seen in PD (Tarsey 1989;Hausner 1986).…”

Section: Discussionmentioning

confidence: 99%

Instrumentally Detected Changes in Motor Functioning in Patients with Low Levels of Antipsychotic Dopamine D2 Blockade

Fitzgerald¹,

Kapur

Caligiuri

et al. 2000

Neuropsychopharmacology

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Increased density of dopamine D2 receptors in the putamen, but not in the caudate nucleus in early Parkinson's disease: a PET study with [11C]raclopride

Cited by 105 publications

References 28 publications

Sequential versus Nonsequential Measurement of Density and Affinity of Dopamine D2 Receptors with [¹¹C]Raclopride: 2: Effects of DAT Inhibitors

Sequential versus Nonsequential Measurement of Density and Affinity of Dopamine D2 Receptors with [¹¹C]Raclopride: 2: Effects of DAT Inhibitors

Estimation of D2-like Receptor Occupancy by Dopamine in the Putamen of Hemiparkinsonian Monkeys

Instrumentally Detected Changes in Motor Functioning in Patients with Low Levels of Antipsychotic Dopamine D2 Blockade

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Increased density of dopamine D2 receptors in the putamen, but not in the caudate nucleus in early Parkinson's disease: a PET study with [11C]raclopride

Cited by 105 publications

References 28 publications

Sequential versus Nonsequential Measurement of Density and Affinity of Dopamine D2 Receptors with [11C]Raclopride: 2: Effects of DAT Inhibitors

Sequential versus Nonsequential Measurement of Density and Affinity of Dopamine D2 Receptors with [11C]Raclopride: 2: Effects of DAT Inhibitors

Estimation of D2-like Receptor Occupancy by Dopamine in the Putamen of Hemiparkinsonian Monkeys

Instrumentally Detected Changes in Motor Functioning in Patients with Low Levels of Antipsychotic Dopamine D2 Blockade

Contact Info

Product

Resources

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Sequential versus Nonsequential Measurement of Density and Affinity of Dopamine D2 Receptors with [¹¹C]Raclopride: 2: Effects of DAT Inhibitors

Sequential versus Nonsequential Measurement of Density and Affinity of Dopamine D2 Receptors with [¹¹C]Raclopride: 2: Effects of DAT Inhibitors