Combination of In Vivo ¹²³IFP-CIT SPECT and Microdialysis Reveals an Antipsychotic Drug Haloperidol-induced Synaptic Dopamine Availability in the Rat Midbrain and Striatum

Synaptic dopamine (DA) is mainly regulated by the presynaptic DA transporter (DAT). Single-photon emission computerized tomography (SPECT) with the DAT radiotracer [¹²³I]FP-CIT assesses changes in synaptic DA availability when endogenous DA displaces [¹²³I]FP-CIT or competes for DAT. Here, we investigated the effects of haloperidol (HAL) and clozapine (CLZ) on [¹²³I]FP-CIT binding in the rat striatum and midbrain to assess the utility of [¹²³I]FP-CIT SPECT to quantify changes in synaptic DA availability. Rats underwent [¹²³I]FP-CIT SPECT after intraperitoneal administration of normal saline (vehicle), HAL (1 and 7 mg/kg), CLZ (10 and 54 mg/kg) and bupropion (BUP, a DAT blocker, 20 and 100 mg/kg). In the striatum and midbrain, percent differences in the nondisplaceable binding potential (BP(ND)) of [¹²³I]FP-CIT compared to the vehicle were calculated for the various drugs and doses. In another experiment, changes in endogenous striatal DA concentration were measured by in vivo microdialysis under the conditions used in the SPECT study. BUP dose-dependently occupied DAT at considerable levels. Compared to the vehicle, HAL decreased [¹²³I]FP-CIT BP(ND) in the striatum (−25.29% and −2.27% for 1 and 7 mg/kg, respectively) and to a greater degree in the midbrain (−58.74% and −49.64% for 1 and 7 mg/kg, respectively), whereas the CLZ-treated group showed a decrease in the midbrain (−38.60% and −40.38% for 10 and 54 mg/kg, respectively) but an increase in the striatum (18.85% and 38.64% for 10 and 54 mg/kg, respectively). Antipsychotic-induced changes in endogenous striatal DA concentrations varied across drugs and doses. The data demonstrate that [¹²³I]FP-CIT SPECT may be a useful preclinical technique for detecting increases in synaptic DA availability in the midbrain and striatum in response to HAL, with results comparable to those of in vivo microdialysis.

Evaluation of Multiple System Atrophy and Early Parkinson's Disease Using (123)I-FP-CIT SPECT / 핵의학분자영상

PURPOSE: We investigated quantification of dopaminergic transporter (DAT) and serotonergic transporter (SERT) on (123)I-FP-CIT SPECT for differentiating between multiple systemic atrophy (MSA) and idiopathic Parkinson's disease (IPD). MATERIALS AND METHODS: N-fluoropropyl-2beta-carbomethoxy-3beta-4-[(123)I]-iodophenylnortropane SPECT ((123)I-FP-CIT SPECT) was performed in 8 patients with MSA (mean age: 64.0+/-4.5yrs, m:f=6:2), 13 with early IPD (mean age: 65.5+/-5.3yrs, m:f=9:4), and 12 healthy controls (mean age: 63.3+/-5.7yrs, m:f=8:4). Standard regions of interests (ROIs) of striatum to evaluate DAT, and hypothalamus and midbrain for SERT were drawn on standard template images and applied to each image taken 4 hours after radiotracer injection. Striatal specific binding for DAT and hypothalamic and midbrain specific binding for SERT were calculated using region/reference ratio based on the transient equilibrium method. Group differences were tested using ANOVA with the postHoc analysis. RESULTS: DAT in the whole striatum and striatal subregions were significantly decreased in both patient groups with MSA and early IPD, compared with healthy control (p<0.05 in all). In early IPD, a significant increase in the uptake ratio in anterior and posterior putamen and a trend of increase in caudate to putamen ratio was observed. In MSA, the decrease of DAT was accompanied with no difference in the striatal uptake pattern compared with healthy controls. Regarding the brain regions where (123)I-FP-CIT binding was predominant by SERT, MSA patients showed a decrease in the binding of (123)I-FP-CIT in the pons compared with controls as well as early IPD patients (MSA: 0.22+/-0.1 healthy controls: 0.33+/-0.19, IPD: 0.29+/-0.19), however, it did not reach the statistical significance. CONCLUSION: In this study, the differential patterns in the reduction of DAT in the striatum and the reduction of pontine (123)I- FP-CIT binding predominant by SERT could be observed in MSA patients on (123)I- FP-CIT SPECT. We suggest that the quantification of SERT as well as DAT using (123)I- FP-CIT SPECT is helpful to differentiate parkinsonian disorders in early stage.

The Discriminating Nature of Dopamine Transporter Image in Parkinsonism: The Competency of Dopaminergic Transporter Imaging in Differential Diagnosis of Parkinsonism: 123I-FP-CIT SPECT Study / 핵의학분자영상

PURPOSE: The aim of this study was to evaluate the discriminating nature of 123I-FP-CIT SPECT in patients with parkinsonism. METHODS: 123I-FP-CIT SPECT images acquired from the 18 normal controls; NC (60.4+/-10.0 yr) and 237 patients with parkinsonism (65.9+/-9.2 yr) were analyzed. From spatially normalized images, regional counts of the caudate, putamen, and occipital lobe were obtained using region of interest method. Binding potential (BP) was calculated with the ratio of specific to nonspecific binding activity at equilibrium. Additionally, the BP ratio of putamen to caudate (PCR) and asymmetric index (ASI) were measured. RESULTS: BPs of NC (3.37+/-0.57, 3.10+/-0.41, 3.23+/-0.48 for caudate, putamen, whole striatum, respectively) had no significant difference with those of essential tremor; ET (3.31+/-0.64, 3.06+/-0.61, 3.14+/-0.63) and Alzheimer's disease; AD (3.33+/-0.60, 3.29+/-0.79, 3.31+/-0.70), but were higher than those of Parkinson's disease; PD (1.92+/-0.74,1.39+/-0.68, 1.64+/-0.68), multiple system atrophy; MSA (2.36+/-1.07, 2.16+/-0.91, 2.26+/-0.96), and dementia with Lewy body; DLB (1.95+/-0.72, 1.64+/-0.65, 1.79+/-0.66)(p<0.005). PD had statistically lower values of PCR and higher values of ASI than those of NC (p<0.005). And PD had significantly lower value of PCR, higher ASI and lower BP in the putamen and whole striatum than MSA (p<0.05). CONCLUSION: Dopamine transporter image of 123I-FP-CIT SPECT was a good value in differential diagnosis of parkinsonism.

The Discriminating Nature of Dopamine Transporter Image in Parkinsonism: The Competency of Dopaminergic Transporter Imaging in Differential Diagnosis of Parkinsonism: 123I-FP-CIT SPECT Study / 핵의학분자영상

PURPOSE: The aim of this study was to evaluate the discriminating nature of 123I-FP-CIT SPECT in patients with parkinsonism. METHODS: 123I-FP-CIT SPECT images acquired from the 18 normal controls; NC (60.4+/-10.0 yr) and 237 patients with parkinsonism (65.9+/-9.2 yr) were analyzed. From spatially normalized images, regional counts of the caudate, putamen, and occipital lobe were obtained using region of interest method. Binding potential (BP) was calculated with the ratio of specific to nonspecific binding activity at equilibrium. Additionally, the BP ratio of putamen to caudate (PCR) and asymmetric index (ASI) were measured. RESULTS: BPs of NC (3.37+/-0.57, 3.10+/-0.41, 3.23+/-0.48 for caudate, putamen, whole striatum, respectively) had no significant difference with those of essential tremor; ET (3.31+/-0.64, 3.06+/-0.61, 3.14+/-0.63) and Alzheimer's disease; AD (3.33+/-0.60, 3.29+/-0.79, 3.31+/-0.70), but were higher than those of Parkinson's disease; PD (1.92+/-0.74,1.39+/-0.68, 1.64+/-0.68), multiple system atrophy; MSA (2.36+/-1.07, 2.16+/-0.91, 2.26+/-0.96), and dementia with Lewy body; DLB (1.95+/-0.72, 1.64+/-0.65, 1.79+/-0.66)(p<0.005). PD had statistically lower values of PCR and higher values of ASI than those of NC (p<0.005). And PD had significantly lower value of PCR, higher ASI and lower BP in the putamen and whole striatum than MSA (p<0.05). CONCLUSION: Dopamine transporter image of 123I-FP-CIT SPECT was a good value in differential diagnosis of parkinsonism.