Striatal Dopamine D2 Receptor Binding Research Articles

Investigating the role of striatal dopamine receptor 2 in motor coordination and balance: Insights into the pathogenesis of DYT1 dystonia

DYT1 or DYT-TOR1A dystonia is early-onset, generalized dystonia. Most DYT1 dystonia patients have a heterozygous trinucleotide GAG deletion in DYT1 or TOR1A gene, with a loss of a glutamic acid residue of the protein torsinA. DYT1 dystonia patients show reduced striatal dopamine D2 receptor (D2R) binding activity. We previously reported reduced striatal D2R proteins and impaired corticostriatal plasticity in Dyt1 ΔGAG heterozygous knock-in (Dyt1 KI) mice. It remains unclear how the D2R reduction contributes to the pathogenesis of DYT1 dystonia. Recent knockout studies indicate that D2R on cholinergic interneurons (Chls) has a significant role in corticostriatal plasticity, while D2R on medium spiny neurons (MSNs) plays a minor role. To determine how reduced D2Rs on ChIs and MSNs affect motor performance, we generated ChI- or MSN-specific D2R conditional knockout mice (Drd2 ChKO or Drd2 sKO). The striatal ChIs in the Drd2 ChKO mice showed an increased firing frequency and impaired quinpirole-induced inhibition, suggesting a reduced D2R function on the ChIs. Drd2 ChKO mice had an age-dependent deficient performance on the beam-walking test similar to the Dyt1 KI mice. The Drd2 sKO mice, conversely, had a deficit on the rotarod but not the beam-walking test. Our findings suggest that D2Rs on Chls and MSNs have critical roles in motor control and balance. The similarity of the beam-walking deficit between the Drd2 ChKO and Dyt1 KI mice supports our earlier notion that D2R reduction on striatal ChIs contributes to the pathophysiology and the motor symptoms of DYT1 dystonia.

Effects of exposure to chronic uncertainty and a sensitizing regimen of amphetamine injections on locomotion, decision-making, and dopamine receptors in rats.

Gambling disorder (GD) is a behavioral addiction that may be linked to alterations in dopamine (DA) systems. Gambling involves chronic exposure to uncertain reward, which can sensitize the activity of DA systems. Here we explored how combinations of Pavlovian and instrumental uncertainty impact DA sensitization and risky decision-making. Experiment 1: 40 rats underwent 66 uncertainty exposure (UE) sessions during which they responded for saccharin. Animal responding was reinforced according to a fixed or variable (FR/VR) ratio schedule that turned on a conditioned stimulus (CS; light), which predicted saccharin on 50% or 100% of trials. Animals responded under one of the four conditions: FR-CS100% (no uncertainty), VR-CS100%, FR-CS50%, and VR-CS50% (maximal uncertainty). DA sensitization was inferred from an enhanced locomotor response to d-amphetamine (d-AMPH; 0.5 mg/kg) challenge. The rat gambling task (rGT) was used to assess decision-making. Experiment 2: 24 rats received 5 weeks of sensitizing d-AMPH or saline doses, followed by locomotor activity and rGT testing. Experiment 3: Effects of UE and a sensitizing d-AMPH regimen on DA D1, D2, and D3 receptor binding were assessed in 44 rats using autoradiography. Compared to FR-CS100%, VR-CS100% and VR-CS50% rats displayed a greater locomotor response to d-AMPH, and VR-CS50% rats demonstrated riskier decision-making. Chronic d-AMPH-treated rats mirrored the effects of VR-CS50% groups on these two indices. Both VR-CS50% and d-AMPH-treated groups had increased striatal DA D2 receptor binding. These results suggest that chronic uncertainty exposure, similar to exposure to a sensitizing d-AMPH regimen, sensitized the function of DA systems and increased risky decision-making.

Sensory Processing in Rhesus Monkeys: Developmental Continuity, Prenatal Treatment, and Genetic Influences.

Neonatal sensory processing (tactile and vestibular function) was tested in 78 rhesus macaques from two experiments. At ages 4-5years, striatal dopamine D2 receptor binding was examined using positron emission tomography. At ages 5-7years, adult sensory processing was assessed. Findings were: (a) prenatal stress exposure yielded less optimal neonatal sensory processing; (b) animals carrying the short rh5-HTTLPR allele had less optimal neonatal sensory scores than monkeys homozygous for the long allele; (c) neonatal sensory processing was significantly related to striatal D2 receptor binding for carriers of the short allele, but not for animals homozygous for the long allele; and (d) there was moderate developmental continuity in sensory processing from the neonatal period to adulthood.

Relationship Between L-DOPA-Induced Reduction in Motor and Exploratory Activity and Striatal Dopamine D2 Receptor Binding in the Rat.

Purpose: The present study assessed the influence of L-DOPA administration on neostriatal dopamine (DA) D2 receptor binding in relation to motor and exploratory behaviors in the rat.Methods: D2 receptor binding was measured in baseline, after challenge with the aromatic L-amino acid decarboxylase inhibitor benserazide, and after challenge with either 5 or 10 mg/kg L-DOPA plus benserazide. Additional rats received injections of saline. For baseline and challenges, striatal equilibrium ratios (V) were computed as estimation of the binding potential. Motor and exploratory behaviors were assessed for 30 min in an open field prior to administration of [123I]IBZM. D2 receptor binding was measured with small animal SPECT 2 h after radioligand administration for 60 min.Results: Both L-DOPA doses significantly reduced D2 receptor binding relative to baseline and led to significantly less ambulation, less head-shoulder motility, and more sitting relative to saline. Moreover, 10 mg/kg L-DOPA induced less head-shoulder motility, more sitting, and more grooming than 5 mg/kg L-DOPA. Analysis of time-behavior curves showed that L-DOPA-treated animals relative to saline exhibited a faster rate of decrease of ambulation frequency and a slower rate of decrease of both duration and frequency of head-shoulder motility from a lower maximum level.Conclusions: The reductions of striatal D2 receptor binding after L-DOPA may be conceived to reflect elevated concentrations of synaptic DA. L-DOPA-treated animals showed less ambulation and less head-shoulder motility than saline-treated animals, indicating an association between less behavioral activity and increased availability of striatal DA. The faster rate of decrease of ambulation frequency and the lower maximum levels of both head-shoulder motility duration and frequency may be interpreted in terms of influence of increased DA availability on behavioral habituation to a novel environment.

Dopamine D1 receptor availability is related to social behavior: A positron emission tomography study

Dysfunctional interpersonal behavior is thought to underlie a wide spectrum of psychiatric disorders; however, the neurobiological underpinnings of these behavioral disturbances are poorly understood. Previous molecular imaging studies have shown associations between striatal dopamine (DA) D2-receptor binding and interpersonal traits, such as social conformity. The objective of this study was to explore, for the first time, the role of DA D1-receptors (D1-Rs) in human interpersonal behavior.Twenty-three healthy subjects were examined using positron emission tomography and the radioligand [11C]SCH23390, yielding D1-R binding potential values. Striatal D1-R binding was related to personality scales selected to specifically assess one dimension of interpersonal behavior, namely a combination of affiliation and dominance (i.e., the Social Desirability, Verbal Trait Aggression and Physical Trait Aggression scales from Swedish Universities Scales of Personality). An exploratory analysis was also performed for extrastriatal brain regions.D1-R binding potential values in the limbic striatum (r=.52; p=.015), associative striatum (r=.55; p=.009), and sensorimotor striatum (r=.67; p=.001) were positively related to Social Desirability scores. D1-R binding potential in the limbic striatum (r=−.51; p=.019) was negatively associated with Physical Trait Aggression scores. For extrastriatal regions, Social Desirability scores showed positive correlations in the amygdala (r=.60; p=.006) and medial frontal cortex (r=.60; p=.004).This study provides further support for the role of DA function in the expression of disaffiliative and dominant traits. Specifically, D1-R availability may serve as a marker for interpersonal behavior in humans. Associations were demonstrated for the same dimension of interpersonal behavior as for D2-R, but in the opposite direction, suggesting that the two receptor subtypes are involved in the same behavioral processes, but with different functional roles.

Treadmill exercise elevates striatal dopamine D2 receptor binding potential in patients with early Parkinson’s disease

We have previously demonstrated changes in dopaminergic neurotransmission after intensive exercise in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse model of Parkinson's disease (PD), including an increase in the dopamine D2 receptor (DA-D2R), using noninvasive PET imaging with the radioligand [18F]fallypride. The purpose of this feasibility and translational study was to examine whether intensive exercise leads to similar alterations in DA-D2R expression using PET imaging with [18F]fallypride in individuals with early-stage PD. In this pilot study, four patients with early-stage PD were randomized to receive intensive exercise (treadmill training sessions three times/week for 8 weeks) or no exercise. Two healthy age-matched individuals participated in treadmill training. Alterations in the DA-D2R binding potential (BP) as a marker for receptor expression were determined using PET imaging with [18F]fallypride. Turning performance in the patients with PD as a measure of postural control and the Unified Parkinson's Disease Rating Scale scores pre-exercise and postexercise were determined. Our data showed an exercise-induced increase in [18F]fallypride BP as well as improved postural control in patients with PD who exercised. Changes in DA-D2R BP were not observed in patients with PD who did not exercise. These results suggest that exercise can lead to neuroplasticity in dopaminergic signaling and contribute to improved function that may be task specific (postural control) in early-stage PD.

Dopamine D2 receptor SPECT in corticobasal syndrome and autopsy-confirmed corticobasal degeneration

BackgroundCorticobasal degeneration (CBD) is a rare neurodegenerative disorder characterized by tau-positive neuronal and glial lesions in the cortex and striatum with neuronal loss in cortical regions and in the substantia nigra. Striatal dopamine D2 receptor binding in autopsy-confirmed CBD has not been studied before. MethodsWe performed D2 receptor single photon emission computerized tomography using 123I-IBZM in nine patients with a clinically diagnosed corticobasal syndrome (CBS) and on ten healthy controls. Two of the patients subsequently came to autopsy and were diagnosed with CBD. ResultsOverall striatal D2 receptor binding was preserved in 8/9 patients, but more asymmetric than in controls. Overall striatal binding in pathologically confirmed CBD was reduced in one case and normal in the other, and was lower contralateral to the clinically more affected side in both. ConclusionThis first study on D2 receptor imaging in autopsy-confirmed CBD demonstrates that loss of postsynaptic striatal neurons in CBD is a variable finding. Given the heterogeneity of our findings in pathology-confirmed cases, D2 receptor imaging seems to be of little practical value in the diagnostic workup of patients with CBS.

Threshold for visual awareness is associated with striatal dopamine D2 receptor binding

Threshold for visual awareness is associated with striatal dopamine D2 receptor binding

Activity-dependent reduction of dopamine D2 receptors during a postnatal critical period of plasticity in rat striatum is not affected by prenatal haloperidol treatment

Motor activity induced in the Circling Training test (CT) during a postnatal (PN) critical period of plasticity (PN30–37) produces a long-lasting decrease in the number of binding sites and mRNA expression levels of the dopamine D2 receptor (D2R) in rat striatum. Prenatal exposure to the antipsychotic haloperidol also decreases postnatal levels of the striatal D2R in the offspring. We examined whether such fetal exposure to haloperidol could affect the activity-dependent reduction of the D2R system during the critical period. Half of the male offspring exposed to either haloperidol (2.5 mg/kg/day), i.p.) or saline during gestational days 5–18 were subjected to the CT during the critical period, while the remaining represented CT control animals. The adult number of binding sites and mRNA expression levels of the striatal D2R at PN90 were not changed by prenatal haloperidol treatment alone. On the other hand, only pups subjected to the CT during the critical period showed decreases in both studied parameters, regardless the prenatal treatment. These findings indicated that the postnatal reduction of the striatal D2R binding induced prenatally by haloperidol does not affect long-lasting activity-dependent plastic changes on the same receptor system elicited by motor activity in an ontogenetic critical period of plasticity in rat striatum.

Relation between Presynaptic and Postsynaptic Dopaminergic Functions Measured by Positron Emission Tomography: Implication of Dopaminergic Tone

Both presynaptic and postsynaptic dopaminergic functions can be estimated by positron emission tomography (PET). While both presynaptic and postsynaptic dopaminergic functions would be regulated by corresponding genes and related to personality traits, the relation between presynaptic and postsynaptic functions in terms of interindividual variation has hardly been investigated. In the present study, both striatal dopamine D(2) receptor binding and endogenous dopamine synthesis rate were measured in the same healthy subjects using PET with [(11)C]raclopride and l-[β-(11)C]DOPA, respectively, and these two parameters were compared. Two PET studies with [(11)C]raclopride and l-[β-(11)C]DOPA were performed sequentially at rest condition on 14 healthy men. For [(11)C]raclopride PET, the binding potential was calculated by the reference tissue model method. For l-[β-(11)C]DOPA PET, the endogenous dopamine synthesis rate was estimated by graphical analysis. A significant negative correlation was observed between the binding potential of dopamine D(2) receptors and endogenous dopamine synthesis rate (r = -0.66, p < 0.05). Although the interindividual variation of binding potential of [(11)C]raclopride would be due to both the interindividual difference in the receptor density and that in the concentration of endogenous dopamine in the synaptic cleft, the negative correlation between parameters for both presynaptic and postsynaptic functions might indicate a compensative relation between the two functions.

Impaired sequence learning in dystonia mutation carriers: a genotypic effect

Abnormalities in motor sequence learning have been observed in non-manifesting carriers of the DYT1 dystonia mutation. Indeed, motor sequence learning deficits in these subjects have been associated with increased cerebellar activation during task performance. In the current study, we determined whether similar changes are also present in clinically manifesting DYT1 carriers as well as in carriers of other primary dystonia mutations such as DYT6. Additionally, we determined whether sequence learning performance and associated brain activation in these subjects correlate with previously described genotype-related abnormalities of cerebellar pathway integrity and striatal D2 dopamine receptor binding. Nineteen DYT1 carriers (10 non-manifesting DYT1: 51.5±15.1 years; nine manifesting DYT1: 46.1±15.1 years) and 12 healthy control subjects (42.8±15.3 years) were scanned with H2(15)O positron emission tomography while performing controlled sequence learning and reference tasks. Eleven DYT6 carriers (four non-manifesting DYT6: 38.0±22.1; seven manifesting DYT6: 35.3±14.2 years) were evaluated during task performance without concurrent imaging. DYT1 and DYT6 carriers also underwent diffusion tensor magnetic resonance imaging for the assessment of tract integrity and 11C-raclopride positron emission tomography to measure caudate/putamen D2 receptor binding. These imaging measures were correlated with sequence learning performance and associated activation responses. Sequence learning deficits of similar magnitude were observed in manifesting and non-manifesting DYT1 carriers. In contrast, learning deficits were not detected in DYT6 carriers, irrespective of clinical penetrance. Affected DYT1 carriers exhibited significant increases in sequence learning-related activation in the left lateral cerebellar cortex and in the right premotor and inferior parietal regions. Increases in premotor cortical activation observed in the mutation carriers correlated with reductions in cerebellar pathway integrity measured using magnetic resonance diffusion tensor imaging and probabilistic tractography. Additionally, the cerebellar tract changes correlated with reductions in dentate nucleus activation recorded during task performance. Sequence learning performance and task-related activation responses did not correlate with striatal D2 receptor binding. In summary, we found that sequence learning deficits and concomitant increases in cerebellar activation are specific features of the DYT1 genotype. The close relationship between reduced cerebellar pathway integrity and increased learning-related activation of the premotor cortex is compatible with the view of DYT1 dystonia as a neurodevelopmental circuit disorder.

Dynamic changes of striatal dopamine D2 receptor binding at later stages after unilateral lesions of the medial forebrain bundle in Parkinsonian rat models

Our previous study regarding the changes of D2 receptor in nigrostriatal dopamine system at an early stage (4 weeks after lesion) indicated a different functional activity of striatal D2 receptor between two different rat parkinsonian models, lesioning with 6-hydroxydopamine in the striatum and in the medial forebrain bundle (MFB). In the present study, we further examined binding of D2 receptor as well as pre-synaptic dopamine transporter (DAT) at later stages (6 months after lesion) both in the striatal and MFB lesion models. The D2 receptor binding in MFB model at 6 months after lesion was significantly lower than that at 4 weeks after lesion, albeit it was still higher than the normal side. The D2 receptor binding in striatal model was decreased to the same extent at both 4 weeks and 6 months after lesion. DAT binding decreased at 6 months after lesion, more profound in MFB model, and the degree of reduction was not different from that at 4 weeks after lesion. These findings indicated different dynamic processes of the D2 receptor and DAT during a longer time observation in the striatal and MFB lesion models. The dynamic changes of D2 receptor activity after lesion should be considered when selecting 6-hydroxydopamine-induced rat parkinsonian models.

Cannabis use and striatal D2 receptor density in untreated first-episode psychosis: An in vivo SPECT study

The biological basis of the association between cannabis-induced dopamine dysregulation and psychosis remains poorly understood. This (123)I-IBZM SPECT study assessed striatal dopamine D2 receptor (D2R) binding in 37 untreated first-episode psychosis (FEP) subjects, and 18 healthy controls. The aim was to examine if there were differences between FEP subjects with (n=14) and without (n=23) cannabis use in uptake ratios in the D2R. Striatal/Frontal cortex (S/F) uptake ratios were obtained. Healthy controls showed the lowest D2R binding ratios. No differences were found in S/F ratios between users and non-users, suggesting similar dopaminergic mechanisms underlying psychotic symptoms in both groups.

Huntington's Disease: Effect of Memantine on FDG-PET Brain Metabolism?

In this open-label pilot study, the authors evaluated the effect of memantine on the distribution of brain glucose metabolism in four Huntington's disease (HD) patients as determined by serial 18-fluoro-deoxyglucose [F(18)]FDG-PET scans over a period of 3-4 months (90-129 days, with one patient choosing to continue treatment over the 18-month follow-up period). The treatment regimen was well tolerated. No significant differences on neuropsychological parameters before and after treatment were detected; but the patient who continued treatment did not deteriorate at 18 months' reevaluation, whereas the three patients who had stopped treatment after 3 to 4 months had minor progression in all cognitive domains on re-evaluation 12 months after the end of treatment.

Reproducibility of Striatal and Thalamic Dopamine D2 Receptor Binding Using [11C]raclopride with High-Resolution Positron Emission Tomography

Positron emission tomography (PET) imaging of small striatal brain structures such as the ventral striatum (VST) has been hampered by low spatial resolution causing partial-volume effects. The high-resolution research tomograph (HRRT) is a brain-dedicated PET scanner that has considerably better spatial resolution than its predecessors. However, its superior spatial resolution is associated with a lower signal-to-noise ratio. We evaluated the test-retest reliability of the striatal and thalamic dopamine D(2) receptor binding using the HRRT scanner. Seven healthy male volunteers underwent two [(11)C]raclopride PET scans with a 2.5-hour interval. Dopamine D(2) receptor availability was quantified as binding potential (BP(ND)) using the simplified reference tissue model. To evaluate the reproducibility of repeated BP(ND) estimations, absolute variability (VAR) and intraclass correlation coefficients (ICCs) were calculated. VAR values indicated fairly good reproducibility and were 3.6% to 4.5% for the caudate nucleus and putamen and 4.5% to 6.4% for the lateral and medial part of the thalamus. In the VST, the VAR value was 5.8% when the definition was made in the coronal plane. However, the ICC values were only moderate, in the range of 0.34 to 0.66, for all regions except the putamen (0.87). Experimental signal processing methods improved neither ICC nor VAR values significantly.

Leptin increases striatal dopamine D2 receptor binding in leptin‐deficient obese (ob/ob) mice

Peripheral and central leptin administration have been shown to mediate central dopamine (DA) signaling. Leptin-receptor deficient rodents show decreased DA D2 receptor (D2R) binding in striatum and unique DA profiles compared to controls. Leptin-deficient mice show increased DA activity in reward-related brain regions. The objective of this study was to examine whether basal D2R-binding differences contribute to the phenotypic behaviors of leptin-deficient ob/ob mice, and whether D2R binding is altered in response to peripheral leptin treatment in these mice. Leptin decreased body weight, food intake, and plasma insulin concentration in ob/ob mice but not in wild-type mice. Basal striatal D2R binding (measured with autoradiography [(3)H] spiperone) did not differ between ob/ob and wild-type mice but the response to leptin did. In wild-type mice, leptin decreased striatal D2R binding, whereas, in ob/ob mice, leptin increased D2R binding. Our findings provide further evidence that leptin modulates D2R expression in striatum and that these effects are genotype/phenotype dependent.

Association between striatal and extrastriatal dopamine D2-receptor binding and social desirability

Research on the biological underpinnings of personality can provide leads to the pathophysiology of psychiatric disorders. In particular, interpersonal aspects of behavior are a common problem during the course of psychiatric illness. Animal research has demonstrated a role for the dopamine system in social behaviour, and recent molecular imaging studies have shown a negative correlation between dopamine D2-receptor binding in the striatum and social desirability. The emotional and cognitive aspects of social behavior suggest involvement of brain regions outside of the striatum, such as limbic structures. The aim of the present study was to explore associations between the personality trait social desirability and dopamine D2-receptor binding in both striatal and extrastriatal brain regions. We examined 16 control subjects with Positron Emission Tomography and the radioligands [11C]raclopride and [11C]FLB 457, in relation to social desirability in the inventory Swedish universities Scales of Personality. [11C]raclopride D2-receptor binding in the striatum showed negative correlations to social desirability scores, corroborating previous findings. Furthermore, a correlation of a higher statistical significance was demonstrated for [11C]FLB 457 binding in the hippocampal–amygdala complex. A separate analysis of social desirability items in relation to a model of interpersonal behaviour revealed that the associations were driven by items reflecting high submissiveness and high affiliation. Taken together with previous evidence on D2-receptor binding and social behaviour, a role for dopaminergic neurotransmission in regulating displays of dominance vs. submissive behaviour is proposed.

Changes in striatal dopamine D2 receptor binding in pre‐clinical Huntington’s disease

Carriers of the Huntington disease (HD) mutation develop a progressive neurodegenerative disorder after a pre-clinical phase. We examined the value of (11)C-raclopride PET (RAC) as a biomarker for pre-clinical HD pathophysiology. In a prospective cohort study with clinical and neuropsychological assessment we collected complete RAC data in 18 pre-clinical mutation carriers (HD-PMC) and 11 controls. Follow-up was 2 years. We calculated striatal RAC binding potential (BP) to measure dopamine D2 receptor availability. No HD-PMC had overt neuropsychological dysfunction. RAC-BP in putamen was abnormal in up to 44% of HD-PMC. The rate of RAC-BP decline (2.6% per year) was not significantly higher than in controls. Follow-up putaminal BP correlated weakly with predicted distance to onset of clinical HD (P = 0.034), but the rate of decline did not. Three HD-PMC developed motor abnormalities suspect for HD but did not show an increased rate of decline of putaminal BP. Many HD-PMC have striatal abnormalities but we found no clearly increased rate of D2 receptor changes around the onset of clinical HD. A longer follow-up of the present study cohort is needed to establish the value of RAC-BP in assessing the risk of clinical conversion from striatal D2 binding data.

No regional difference in dopamine D2 receptor occupancy by the second-generation antipsychotic drug risperidone in humans: a positron emission tomography study

The effects of antipsychotic drugs have generally been considered to be mediated by blockade of dopamine D2 receptors. The concept of limbic and cortical selectivity of second-generation antipsychotics, i.e. higher dopamine D2 receptor occupancy in the cerebral cortices than in the striatum, has been suggested to explain their clinical efficacy with lower incidence of extrapyramidal side-effects. In this study, regional distribution of dopamine D2 receptor occupancy by risperidone was determined in order to elucidate the limbic and cortical selectivity of second-generation antipsychotics. Striatal and extrastriatal dopamine D2 receptor binding at baseline and after oral administration of 2 mg risperidone were measured in ten healthy men by positron emission tomography (PET) using different tracers with different affinity for the receptors, [11C]raclopride and [11C]FLB 457, respectively. Striatal and extrastriatal occupancies of dopamine D2 receptors were calculated for each brain region. Occupancies of dopamine D2 receptors were about 70% and 60% in the striatum and extrastriatum, respectively. A simulation study showed that non-negligible specific binding in the reference region (cerebellum), could cause systemic underestimation of occupancy in [11C]FLB 457 PET studies, indicating that occupancies in both the striatum and extrastriatum may not have differed. Among the extrastriatal regions including limbic and neocortical regions, no significant regional differences in dopamine D2 receptor occupancy were observed. Thus, limbic and cortical selectivity was not observed by one of the second-generation antipsychotics, risperidone.

Kinetic analyses of [123I]IBZM SPECT for quantification of striatal dopamine D2 receptor binding: A critical evaluation of the single-scan approach

BackgroundDopamine-D2 receptor imaging with single-photon emission computed tomography (SPECT) and [123I]IBZM is of great interest for basic and applied neurosciences. However, the use of kinetic analyses for quantification of dynamic [123I]IBZM SPECT and the validity of the commonly employed single-scan pseudo-equilibrium analysis (PsEA) have not been appropriately investigated. The present study addresses these shortcomings. MethodsTen movement disorder patients underwent dynamic SPECT (142 min) after single-bolus [123I]IBZM injection. Kinetic analyses comprise: simplified reference tissue model (SRTM), multi-linear reference tissue model (MRTM), their two-parameter versions (SRTM2/MRTM2) and non-invasive graphical analysis (NIGA). Simplified single-scan analyses were performed at peak time of specific binding (peak-equilibrium analysis, PEA) and during pseudo-equilibrium (PsEA). ResultsSRTM and MRTM are compromised by the high noise level of dynamic SPECT. SRTM2 and MRTM2 yielded reliable binding potential estimates that agreed excellently (mean difference=−0.1±1.0%, R2>0.99). Concordance between SRTM/MRTM and SRTM2/MRTM2 was high in cases in which SRTM/MRTM provided reliable results (SRTM2 or MRTM2 vs. SRTM: 3.7±5.0%, R2=0.88). NIGA was affected by a negative bias (−9.1±6.3%, R2=0.75; MRTM2 as reference) or high variability (−1.2±7.4%, R2=0.71) for analyses without and with inclusion of the k2′-term, respectively. PsEA showed a positive bias and low correlation in comparison with SRTM2/MRTM2 (7.6±10.8%, R2=0.59), which was considerably improved for PEA (−2.7±7.6%, R2=0.72). MRTM2 provided parametric images with minimal bias suited for voxel-wise statistical analyses. ConclusionsMRTM2 and SRTM2 can be reliably applied to dynamic [123I]IBZM SPECT. PEA is a suitable method for clinical routine, while our results discourage the use of PsEA (current clinical standard).