Evaluation of [123I]IBZM pinhole SPECT for the detection of striatal dopamine D2 receptor availability in rats

Single photon emission computed tomography (SPECT) and MRI coregistration have been assessed to characterize striatal dopamine D2/D3 receptor (D2/D3R) availability in rats following injection of the D2 and D3R radioligand [123I] iodobenzamide ([123I]IBZM). High-resolution SPECT data were obtained with a pinhole collimator. In order to precisely estimate brain regions of low radioligand uptake, SPECT images were coregistered onto a MRI template with high accuracy (maximum mismatch 1.1 mm). To evaluate an adequate dose of radioligand to be administered without exceeding the radioligand-to-receptor occupancy >5% and to define an appropriate time period for image acquisition, three untreated groups of animals received 29.6, 37, and 44.4 MBq of [123I]IBZM and underwent five consecutive SPECT acquisitions lasting 64 min each. Ratio calculations between specific striatal radioligand uptake and nondisplaceable cerebellar uptake revealed a secular equilibrium between 75 and 355 min post-tracer application in all three animal groups. Consequently, since the highest regional uptake values were obtained in the animal group receiving 44.4 MBq [123I]IBZM, this injection dose was considered to be appropriate. Finally, the capacity of the imaging method to detect distinct severity levels of striatal dopamine D2/D3 receptor loss was tested in a low, medium, and high dose quinolinic acid (QA) animal model of Huntington's disease. Motor impairment indicative of striatal dysfunction was monitored using amphetamine-induced rotational behavior and locomotor activity. Loss of striatal D2/D3R bearing medium-sized spiny neurons was assessed by DARPP-32 immunohistochemistry and compared to [123I]IBZM binding. Optical density measures of DARPP-32 immunohistochemistry demonstrated QA dose-dependent mild to subtotal unilateral striatal lesions ranging from 29.4% to 96.9% when compared to the nonlesioned side. Linear regression analysis showed that measurements of striatal DARPP-32 optical density and striatal [123I]IBZM uptake of the lesioned side were highly correlated (r2=0.83; P<0.001) whereas correlation with locomotor activity was less tight (r2=0.23; P<0.05; amphetamine-induced rotational behavior was not significantly correlated). This is the first study to demonstrate that in vivo [123I]IBZM SPECT and MRI coregistration are highly sensitive and, in contrast to behavioral measures, accurately detect mild to subtotal striatal lesions by measuring loss of D2/D3R availability. SPECT-MRI-based estimation of regional [123I]IBZM uptake provides a cost effective and widely available in vivo imaging technique for assessing striatal integrity in animal studies.     

Rigidity and bradykinesia reduce interlimb coordination in Parkinsonian gait

OBJECTIVE: To assess the influence of rigidity and bradykinesia and the extent of dopaminergic degeneration on interlimb coordination during walking in early, drug-naive patients with Parkinsons disease (PD). DESIGN: The interlimb coordination was examined during a systematic manipulation of walking speed on a treadmill. The phase relations between arm and leg movements were related to the clinical measures of rigidity and bradykinesia as well as to the extent of dopaminergic degeneration. SETTING: Movement disorders outpatient clinic (including motion analysis laboratory) and a nuclear medicine department of a university hospital. PARTICIPANTS: Twenty-nine early and drug-naive PD patients. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The interlimb coordination during walking was evaluated by studying the (continuous) relative phase relations between movements of arms and legs. The clinical assessment of rigidity and bradykinesia was performed by using the Unified Parkinson Disease Rating Scale. The dopaminergic degeneration was expressed as striatal 2beta-carboxymethoxy-3beta-(4-iodophenyl) tropane (beta-CIT) single-photon emission computed tomography (SPECT) binding. RESULTS: The mean relative phase between arm and leg movements increased significantly with walking speed in all patients. Significant correlations were found between the rigidity and bradykinesia and the coordination measures ( P 相似文献   

Preserved Extrastriatal 123I-FP-CIT Binding in Scans Without Evidence of Dopaminergic Deficit (SWEDD)

Purpose

Scans without evidence of dopaminergic deficit (SWEDD) have been initially described in a minority of subjects with suspected Parkinson’s disease (PD). Although a highly controversial entity, longitudinal studies showed that SWEDD cases mostly involve non-degenerative conditions mimicking PD or misattribution of scan images to normal status. Using the Parkinson’s Progression Markers Initiative (PPMI) cohort, we undertook a case-controlled analysis of [123I]N-ω-fluoropropyl-2β-carbomethoxy-iodophenyl nortropane ([123I]FP-CIT) single photon emission computed tomography (SPECT) images to measure extrastriatal serotonergic transporter (SERT) density in SWEDD and PD.

Procedures

We included 37 SWEDD cases (mean age 60 years, 33 % female) with available [123I]FP-CIT SPECT imaging and high-resolution T1-weighted magnetic resonance imaging (MRI) for coregistration. Sixty-one controls and 62 similarly aged PD subjects were included for group comparisons. Regional [123I]FP-CIT was extracted with PETPVE12 using geometric transfer matrix and partial volume effect correction.

Results

PD subjects showed significantly lower [123I]FP-CIT binding in both striatal (caudate nucleus and putamen) and extrastriatal regions (pallidum and insula) compared with controls and SWEDD (all between-group p?<?0.0001). PD group also showed lower binding in the thalamus relative to controls (p?=?0.007). Receiver operating characteristics (ROC) area under the curve (AUC) did not show a significant difference when using extrastriatal region in addition to striatal ROIs for the separation of SWEDD and PD (95 % ROC-AUC for both methods, p?=?0.52). In addition, striatal [123I]FP-CIT binding contralateral to the clinically more affected side was usually lower for PD (>?75 %) but not for SWEDD (<?49 %, p?<?0.002). No significant difference regarding [123I]FP-CIT binding was observed between SWEDD and controls.

Conclusion

These findings corroborate the view that SWEDD cases represent a heterogeneous group of conditions not involving dopaminergic and serotonergic terminals. Further studies are warranted to be assessed whether using extrastriatal [123I]FP-CIT evaluation can be of help in the assessment of degenerative parkinsonism.

     

Quantitative [(123)I]FP-CIT pinhole SPECT imaging predicts striatal dopamine levels, but not number of nigral neurons in different mouse models of Parkinson's disease

Single photon emission computed tomography (SPECT) using [(123)I]FP-CIT as radioligand for the dopamine transporter has become a widely used tool to monitor the integrity of the nigrostriatal dopaminergic projection in Parkinson's disease (PD). Previous studies with pinhole SPECT in small animals have demonstrated that the striatal [(123)I]FP-CIT binding indeed correlates with the striatal dopamine transporter protein level. It is unclear, however, if there is a stable relationship between the striatal [(123)I]FP-CIT binding and other functionally important parameters of the nigrostriatal system, such as the striatal dopamine levels and the number of dopaminergic neurons in the substantia nigra. To assess this question experimentally, we studied two different mouse models of PD, namely a mild 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine intoxication paradigm, to model mild nigrostriatal damage and the intrastriatal 6-hydroxydopamine paradigm to model more advanced nigrostriatal damage. Our data demonstrate that the striatal [(123)I]FP-CIT binding measured by SPECT in vivo precisely predicts the striatal dopamine concentrations, but does not necessarily correlate with the nigral dopaminergic cell number. Thus, the present work underscores that FP-CIT SPECT does only allow judging the integrity of the striatal dopaminergic nerve terminals, but not the nigral dopaminergic cells in PD. This finding may have significant impact on the use of [(123)I]FP-CIT SPECT as a surrogate marker for clinical trials aimed at measuring neuroprotection.     

Evaluation of striatal dopamine transporter function in rats by in vivo beta-[123I]CIT pinhole SPECT

Striatal dopamine transporter (DAT) function was evaluated in rats by in vivo SPECT-MRI coregistration using the radioligand 2-beta-carbomethoxy-3-beta-(4-[123I]iodophenyl)tropane (beta-[123I]CIT). The reconstructed transaxial resolution of 3.5 mm full width at half-maximum and the system sensitivity of 0.081 c/s/kBq using a 2.0-mm pinhole collimator aperture provided adequate spatial detail and sufficient sensitivity for imaging striatal beta-[123I]CIT uptake. SPECT images, coregistered onto a MRI template, showed high accuracy in the coronal and transverse planes (maximum mismatch of 1.3 mm). Following estimation of the in vivo binding equilibrium of beta-[123I]CIT in the healthy rat striatum, we evaluated the 6-hydroxydopamine-induced loss of striatal DAT function using beta-[123I]CIT SPECT and MRI coregistration and correlated these findings with dopaminergic cell counts in the substantia nigra pars compacta using TH immunohistochemistry. A subtotal unilateral DAT deficit was detected by beta-[123I]CIT SPECT in all animals which correlated significantly with the cell counting of the remaining dopaminergic neurons. beta-[123I]CIT pinhole SPECT provides a powerful and widely available tool for in vivo investigations of rat striatal DAT function. In contrast to classical autoradiography, the present method will be helpful in imaging dynamic changes of neurotransmission in the CNS by virtue of serial study designs. Depending on SPECT ligand availability, a wide range of other CNS receptors may be imaged as well using the presented in vivo technique.     

SPECT and PET in Parkinson's disease

In Parkinson's disease(PD) cerebral blood flow and glucose metabolic rate measurements using SPECT and PET have demonstrated functional abnormality in basal ganglia-thalamocortical and its related circuits. [123I] IBF SPECT and [11C] raclopride PET seemed promising tools to assessing D2 receptor status in humans. Studies of D2 status have demonstrated normal or increased receptor density in PD and decreased receptor density in multiple system atrophy. Marked differences of the dopamine transporters located on dopaminergic terminals in the striatum has been demonstrated in healthy controls and PD patients using SPECT. The correlation of SPECT measures of dopamine transporters and motor severity suggests that this may be an useful marker of disease severity in PD.     

Pinhole SPECT imaging of dopamine transporters correlates with dopamine transporter immunohistochemical analysis in the MPTP mouse model of Parkinson's disease

The in vivo analysis of dopaminergic degeneration in animal models of Parkinson's disease (PD), using pinhole single photon emission computed tomography (SPECT), ideally should afford a serial study design, enabling the analysis of the degenerative process as well as the potential neuroprotective and/or restorative properties of drugs over time in living animals. Previously, we demonstrated that striatal dopamine transporter (DAT) levels in rats could be analyzed reproducibly, using pinhole SPECT with the DAT probe [(123)I]N-omega-fluoropropyl-2beta-carbomethoxy-3beta-{4-iodophenyl}nortropane (FP-CIT). However, the capacity of this approach to accurately detect a range of striatal DAT levels in the most widely used animal model of PD, i.e., the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mouse, remains to be determined. For this purpose, various levels of DAT were induced by treating c57BL/6J mice for 1, 3, or 5 days with MPTP (25 mg/kg ip), respectively. [(123)I]FP-CIT SPECT scans were performed 5 days after the last MPTP injection. Mice were perfused 6 days after the last MPTP injection, and the SPECT data were compared to ex vivo striatal and nigral DAT levels as measured by immunohistochemistry within the same animals. The analysis of striatal DAT levels using SPECT and DAT immunohistochemistry yielded highly comparable results on the percentage of DAT reduction in each MPTP group. The in vivo data showed a decrease of specific striatal to non-specific binding ratios by 59%, 82%, and 76% in mice treated for 1, 3, and 5 days, respectively. Moreover, a strong, positive correlation was observed between the in vivo and ex vivo parameters. The present study provides the first evidence that [(123)I]FP-CIT pinhole SPECT allows the accurate detection of a range of striatal DAT (i.e., losses of approximately 60-80%) levels in mice. Since such large dopaminergic lesions could be detected, this SPECT method may at least be useful for analyzing neuroprotective treatment with a clear-cut positive (i.e., complete protection) or negative (i.e., not any protection) effect. Whether this method is also useful for analyzing more subtle effects of neuroprotective treatment (partial protection) remains to be established, by studying mice with small dopaminergic lesions.     

Simultaneous [99mTc]TRODAT-1 and [123I]ADAM Brain SPECT in Nonhuman Primates

Purpose  This study examined the feasibility of simultaneous dopamine and serotonin transporter imaging using [¹²³I]ADAM and [^99mTc]TRODAT-1 single photon emission computed tomography (SPECT). Procedures  Simultaneous [¹²³I]ADAM (185 MBq) and [^99mTc]TRODAT-1 (740 MBq) SPECT was performed in three age-matched female Formosan rock monkeys. An asymmetric energy window was used for dual, and symmetric energy windows were used for single-isotope imaging. Oral fluoxetine (20 mg) and intravenous methylphenidate HCl (1 mg/kg) were given 24 h and 10 min, respectively, before dual-isotope SPECT to test imaging specificities of [¹²³I]ADAM and [^99mTc]TRODAT-1. Results  Comparable image quality and uptake ratios between dual- and single-isotope SPECT scans were found. Dual-isotope SPECT in fluoxetine-pretreated monkeys showed decreased uptake of [¹²³I]-ADAM, but not of [^99mTc]TRODAT-1. Dual-isotope SPECT in methylphenidate-pretreated monkeys showed decreased [^99mTc]TRODAT-1 uptake without affecting [¹²³I]-ADAM uptake. Conclusion  Simultaneous [¹²³I]-ADAM and [^99mTc]TRODAT-1 SPECT appears promising in nonhuman primates and may provide a suitable preclinical model with further clinical implications.     

Transcranial Sonography and I-FP-CIT Single Photon Emission Computed Tomography in Movement Disorders

Diagnosis of Parkinson's disease (PD) can be difficult in the early stages of the disease. The aim of the study described here was to assess the correlation between transcranial sonography (TCS) and ¹²³I-FP-CIT ([¹²³I]ioflupane, N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-[¹²³I]iodophenyl)nortropane) SPECT (single photon emission computed tomography) findings and the diagnosis of PD. A total of 49 patients were enrolled in the study: 29 patients with PD, 7 patients with other parkinsonian syndromes, 11 patients with essential tremor and 2 with psychogenic movement disorder. Substantia nigra echogenicity was measured using TCS. SPECT was performed using DaTSCAN ([¹²³I]ioflupane). TCS and SPECT findings were correlated in 84% of patients, with κ = 0.62 (95% confidence interval: 0.38–0.86). TCS-measured substantia nigra echogenicity and SPECT-measured striatal binding ratio were negatively correlated (r = –0.326, p = 0.003). TCS/SPECT sensitivity, specificity and positive and negative predictive values for the diagnosis of PD were 89.7%/96.6%, 60.0%/70.0%, 76.5%/82.4% and 80.0%/93.3%, respectively. Both positive TCS and SPECT findings correlated significantly with the diagnosis of PD (κ = 0.52, 95% confidence interval: 0.27–0.76, and κ = 0.69, 95% confidence interval: 0.49–0.90, respectively).     

The application of statistical parametric mapping to 123I-FP-CIT SPECT in dementia with Lewy bodies, Alzheimer's disease and Parkinson's disease

Dopaminergic loss can be visualised using (123)I-FP-CIT single photon emission computed tomography (SPECT) in several disorders including Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Most previous SPECT studies have adopted region of interest (ROI) methods for analysis, which are subjective and operator-dependent. The purpose of this study was to investigate differences in striatal binding of (123)I-FP-CIT SPECT using the automated technique of statistical parametric mapping (SPM99) in subjects with DLB, Alzheimer's disease (AD), PD and healthy age-matched controls. This involved spatial normalisation of each subject's image to a customised template, followed by smoothing and intensity normalisation of each image to its corresponding mean occipital count per voxel. Group differences were assessed using a two-sample t test. Applying a height threshold of P 相似文献   

Nicotinic alpha4beta2 receptor binding in dementia with Lewy bodies using 123I-5IA-85380 SPECT demonstrates a link between occipital changes and visual hallucinations

INTRODUCTION: To investigate in vivo differences in the distribution of alpha4beta2 subtypes of nAChR using the ligand (123)I-5-Iodo-3-[2(S)-2-azetidinylmethoxy] pyridine (5IA-85380) and single photon emission computed tomography (SPECT) in DLB and similarly aged controls. METHODS: Thirty-one subjects (15 DLB and 16 controls) underwent (123)I-5IA-85380 and perfusion ((99m)Tc-exametazime) SPECT scanning. Patient scans were compared to scans of control subjects on a voxel-by-voxel basis using SPM2. RESULTS: Compared to controls, significant reductions in relative (123)I-5IA-85380 uptake were identified in frontal, striatal, temporal and cingulate regions in DLB. Elevation of scaled (123)I-5IA-85380 uptake in occipital cortex was observed in DLB relative to controls, as well as being associated with DLB subjects with a recent history of visual hallucinations. Changes in (123)I-5IA-85380 SPECT in DLB were different from perfusion. CONCLUSION: Reductions in normalised (123)I-5IA-85380 uptake in DLB were distinct from their perfusion deficits. Significant increase in occipital lobe uptake was present in DLB, a change most pronounced in subjects with a recent history of visual hallucinations. The findings directly link cholinergic changes in occipital lobe to visual hallucinations in DLB.     

Dopamine D2-receptor imaging with 123I-iodobenzamide SPECT in migraine patients abusing ergotamine: does ergotamine cross the blood brain barrier?

Two migraine patients were studied by in vivo SPECT using the dopamine D2-receptor specific radioligand ¹²³I-3-iodo-6-methoxybenzamide (¹²³I-IBZM) during ergotamine abuse and after withdrawal. Results were compared with 15 healthy controls. Striatum/cerebellum and striatum/occipital cortex ratios of count rate density were calculated as a semiquantitative measurement for striatal dopamine D2-receptor binding potential. No differences were found in striatal uptake of ¹²³I-IBZM between healthy controls and the patients when on or off ergotamine. Preliminary evidence suggests that ergotamine may not occupy striatal dopamine D2-receptors to a large extent and thus may not cross the blood brain barrier in large quantities.     

In vivo evaluation of the dopaminergic neurotransmission system using [123I]FP‐CIT SPECT in 6‐OHDA lesioned rats

The 6‐hydroxydopamine (6‐OHDA) rodent model of Parkinson's disease (PD) has been used to evaluate the nigrostriatal pathway. The aim of this work was to explore the relationship between the degree of 6‐OHDA‐induced dopaminergic degeneration and [¹²³I]FP‐CIT binding using single photon emission computed tomography (SPECT). Fourteen rats received a 6‐OHDA injection (4 or 8 µg) into the left medial forebrain bundle. After 3 weeks, magnetic resonance imaging and scans with a small‐animal SPECT system were performed. Finally, the nigrostriatal lesion was assessed by immunohistochemical analysis. Immunohistochemical analysis confirmed two levels of dopaminergic degeneration. Lesions induced by 6‐OHDA diminished the ipsilateral [¹²³I]FP‐CIT binding by 61 and 76%, respectively. The decrease in tracer uptake between control and lesioned animals was statistically significant, as was the difference between the two 6‐OHDA lesioned groups. Results concluded that [¹²³I]FP‐CIT SPECT is a useful technique to discriminate the degree of dopaminergic degeneration in a rat model of PD. Copyright © 2014 John Wiley & Sons, Ltd.     

脑多巴胺转运体显像在诊断帕金森病中的应用

目的研究^99mTc-TRODAT-1多巴胺转运体（DAT）SPECT显像诊断和评价帕金森病（PD）严重程度的意义。方法对12例健康自愿者、38例帕金森病患者行^99mTc-TRODAT-1SPECT断层显像,利用感兴趣区方法在横断层上应用半定量的计算机感兴趣区技术分别勾画最清楚的连续三层,取其平均值计算帕金森病患者和健康对照者的纹状体（尾状核、壳核）与本底[（小脑＋枕叶）/2]部位的DAT比值,分别代表相应部位的多巴胺转运蛋白功能水平。对PD患者进行UPDRS评分和Hoehn-Yahr分级。结果帕金森病患者双侧纹状体的多巴胺转运蛋白功能均低于健康对照者,差异有统计学意义（t分别=31.51、27.99,P均〈0.05）,并以患侧肢体或最先受累肢体对侧多巴胺转运蛋白功能降低为甚,差异有统计学意义（t=4.80,P〈0.05）,尤其是在Hoehn-YahrI期帕金森病患者。使用相关分析表明DAT摄取比值同UPDRS评分、Hoehn-Yahr分级都存在良好的相关性（t分别=12.45、2.21,P均〈0.05）。结论^99mTc-TRODAT-1SPECT脑显像为提高帕金森病的诊断准确性提供了一种行之有效的手段,对于评价帕金森病的严重程度有益。     

In vivo SPECT imaging of vesicular acetylcholine transporter using [(123)I]-IBVM in early Alzheimer's disease

INTRODUCTION: Little is known about cholinergic activity in the early stage of Alzheimer's disease. We investigated differences in the distribution of vesicular acetylcholine transporter, using [(123)I]-iodobenzovesamicol ([(123)I]-IBVM) and Single Photon Computed Tomography (SPECT), in early AD and age-matched controls. MATERIALS AND METHODS: Sixteen subjects (8 controls, 8 AD) underwent [(123)I]-IBVM SPECT scanning, T1-weighted anatomic scan by Magnetic Resonance (MR) imaging and Mini-Mental State Evaluation (MMSE). Image analysis, using Statistical Parametric Mapping (SPM 02), involved coregistration of each SPECT image to the MR scan, followed by a spatial normalisation to the Montreal Neurological Institute standard brain and a smoothing of each SPECT image. Group effects and correlation were assessed using two sample t-tests and linear regression respectively. Atrophy difference between the two groups was assessed by voxel-based morphometry of each MR scan using two sample t-tests. RESULTS: MMSE values were significantly different between AD and controls. Relative to controls, a significant decrease in [(123)I]-IBVM binding (47-62%) was apparent in AD subjects in cingulate cortex and parahippocampal-amygdalo?d complex. These patterns appeared to be independent of atrophied areas. CONCLUSION: These results strongly suggest that a cholinergic degeneration occurs in the early stage of AD and could be involved in the impairment of the cognitive functions. Imaging of cholinergic neurons used here could be effective in identifying potential cholinergic treatment responders.     

Comparison of two methods for the analysis of [18F]6-fluoro-L-m-tyrosine PET data

PET and [18F]fluoro-L-m-tyrosine (FMT) have been used to quantify presynaptic striatal dopamine (DA) function in Parkinson disease (PD) and in primate models of PD. While dynamic imaging and a metabolite-corrected blood input function can be used to determine striatal FMT uptake rate constants (Ki), a simpler analytic approach using shorter imaging times is desirable for clinical studies. We compared the utility of using striatal Ki values versus striatal count ratios in two groups of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys. Striatal DA content was also measured in one of the groups to evaluate the relationship between the PET measures and an independent measure of striatal dopamine. Striatal Ki values were significantly correlated with striatal count ratios using the cerebellum as the denominator. Both Ki values and ratios were also correlated with striatal DA content. In addition, putamen-cerebellum ratios and putamen Ki values showed similar separation between baseline and post-MPTP values. These findings suggest that a simple ratio approach to analyzing FMT PET data may be a useful alternative to a kinetic approach especially for clinical applications.     

Spatial Inhomogeneity of Cardiac Norepinephrine Transport Protein and Meta-[123I]Iodobenzylguanidine Uptake in Swine Myocardial Tissue

Purpose

The aim of the present study was to evaluate the expression of the cardiac norepinephrine transporter (NET) in the left ventricle (LV) of healthy pigs and its relationship with regional meta-[¹²³I]iodobenzylguanidine ([¹²³I]MIBG) myocardial uptake.

Procedures

Experiments were performed on animals injected with [¹²³I]MIBG and acquired 2 h later using an ultrafast CZT gamma camera to assess the regional myocardial uptake. After image acquisition, animals were euthanized; the heart was quickly excised and underwent to an ex vivo single photon emission tomography (SPECT) imaging. Four small samples of tissue were then harvested from mid-walls and apex of the left ventricle; NET densities were evaluated and further normalized for protein loading per cardiac region.

Results

Three variants of NET protein with different molecular weights were detected. The expression of NET was not homogenous in the LV, with the highest density in the inferior wall and the lowest one in the apical area. The regional in vivo [¹²³I]MIBG uptake revealed an analogous trend, showing a good linear relationship with NET expression. Parallel results were obtained from the ex vivo study.

Conclusion

This study elucidates the expression of three different variants of NET proteins into the left ventricular myocardium of a healthy pig. NET expression into the LV was not homogeneous and paralleled by differences in regional [¹²³I]MIBG uptake. Moreover, the correlation and the agreement between measurements of regional expression of NET variants and [¹²³I]MIBG uptake represent a relevant finding for inferences about NET expression in the context of clinical imaging.

     

Adrenergic innervation of the myocardium in patients with cardiac syndrome X]

11 syndrome X patients and 8 healthy controls were investigated by myocardial scintigraphy (SPECT) with 123-I-MIBG. Regional defects in cardiac 123-I-MIBG uptake were found in 90% syndrome X patients. Total cardiac 123-I-MIBG uptake appeared significantly higher in syndrome X patients. Perfusion defects on stress 99m-Tc-MIBI scintigraphy were found in 10 syndrome X patients who had also abnormal 123-I-MIBG scintigrams. It is suggested that impairment of efferent cardiac adrenergic nerve fiber function in syndrome X patients may contribute to pathophysiologic and clinical features of syndrome X.     

Altered dopamine D2 receptor binding in atypical facial pain

Animal studies suggest that the dopaminergic system plays a role in central pain modulation. We have previously demonstrated with positron emission tomography (PET) that striatal dopaminergic hypofunction may be involved in the burning mouth syndrome. The aim of the present study was to evaluate the nigrostriatal dopaminergic system in patients with atypical facial pain using PET. In seven patients with atypical facial pain, striatal presynaptic dopaminergic function was assessed with [18F]FDOPA and dopamine D1 and D2 receptor availabilities with [11C]NNC 756 and [11C]raclopride, respectively. The results were compared with those of healthy controls. A quantitative region-of-interest analysis showed that the uptakes of [18F]FDOPA and [11C]NNC 756 did not differ between patients and controls. There was a tendency of increased D2 receptor availability in the left putamen (P=0.056), and the D1/D2 ratio in the putamen was decreased bilaterally by 7.7% (P=0.002) in patients when compared to controls. In a voxel-based analysis, the uptake of [11C]raclopride was increased in the left putamen (P=0.025). In conclusion, the increase in D2 receptor availability in the left putamen and the decrease in D1/D2 ratio imply that alterations in the striatal dopaminergic system as evaluated by PET may be involved in chronic orofacial pain conditions.     

D‐ and L‐[123I]‐2‐I‐phenylalanine show a long tumour retention compared with D‐ and L‐[123I]‐2‐I‐tyrosine in R1M rhabdomyosarcoma tumour‐bearing Wag/Rij rats

The aim of this study was the comparison of the tumour uptake and the long‐term retention of [¹²³I]‐2‐I‐L ‐phenylalanine and [¹²³I]‐2‐I‐D ‐phenylalanine with those of [¹²³I]‐2‐I‐L ‐tyrosine and [¹²³I]‐2‐I‐D ‐tyrosine in R1M rhabdomyosarcoma tumour‐bearing rats. The biodistribution of the radioactivity as a function of time in R1M tumour‐bearing rats was measured by planar gamma camera imaging (dynamic and static). If dissection was applied, the activity in the tumours and tissues of interest was measured by gamma counting. [¹²³I]‐2‐iodo‐L ‐phenylalanine, [¹²³I]‐2‐iodo‐D ‐phenylalaine, [¹²³I]‐2‐I‐L ‐tyrosine showed a considerable tumour uptake reaching a maximum between 10 and 30 min. At 30 min p.i. the differential uptake ratio values of this uptake were, respectively, 2.1, 2.3, 2.5 and 1.7. The activity in the tumour was shown to be related to a tumour cell uptake and not to an increased blood pool activity. All the tracers showed a clearance from the blood to the bladder without renal retention. At longer times both L ‐ and D ‐ [¹²³I]‐2‐I‐tyrosine were cleared for a large part from the tumours and the body. [¹²³I]‐2‐I‐L ‐Phe and [¹²³I]‐2‐I‐D ‐Phe showed a considerable and equal retention in the tumours: as compared with 0.5 h, 91% at 24 h and 80% at 48 h. This was related to the longer retention of activity in the blood pool noticed for these compounds (81% at 24 h and 65% at 48 h). The tumour‐to‐background ratio increased with 25% at those longer times. At short times all the tracers were taken up to a considerable extent in the tumours. In the R1M‐bearing Wag/Rij rat model only [¹²³I]‐2‐I‐L ‐phenylalanine and [¹²³I]‐2‐I‐D ‐phenylalanine showed an especially high retention at long times without any significant difference between the enantiomers. Copyright © 2007 John Wiley & Sons, Ltd.