Comparison of iodine-123 labelled 2β-carbomethoxy-3β-(4-iodophenyl)tropane and 2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)nortropane for imaging of the dopamine transporter in the living human brain

Several cocaine congeners are of potential for imaging the dopamine transporter (DAT). Previous studies have shown that iodine-123 labelled 2-carbomethoxy-3-(4-iodophenyl)tropane ([¹²³I]-CIT) is a promising radiotracer for imaging the serotonin (5-HT) and dopamine (DA) transporters in the living human brain with single-photon emission tomography (SPET). [¹²³I]-CIT was found to be not very practical for 1-day DAT imaging protocols since peak DAT uptake occurs later than 8 h. Here we report a pilot comparison of [¹²³I]-CIT and 2-carbomethoxy-3-(4-iodophenyl)-N-(3-fluoropropyl)nortropane ([¹²³I]-CIT FP), using SPET imaging in four healthy male subjects. Peak uptake of [¹²³I]-CIT-FP into the basal ganglia occurred earlier (3–4 h after injection of tracer) than that of [¹²³I]-CIT (>8 h). However, the specific DAT binding of [¹²³I]-CIT-FP in the basal ganglia was somewhat less (0.813±0.047) than that of [¹²³I]-CIT (0.922±0.004). Imaging quality is excellent with both tracers and they are potentially of value for brain imaging in various neuropsychiatric disorders.     

Comparison of [123I]ß-CIT and [123I]IPCIT as single-photon emission tomography radiotracers for the dopamine transporter in nonhuman primates

Single-photon emission tomographic (SPET) imaging with the radiotracer [¹²³I]2-carbomethoxy-3-(4-iodophenyl)tropane ([¹²³I]-CIT) has been reported to be a useful in vivo measure of dopamine (DA) transporters. However, in addition to its high DA transporter affinity,-CIT also binds with high affinity to serotonin (5-HT) transporters. 2-Carboisopropoxy-3-(4-iodophenyl)tropane (IPCIT) has been demonstrated by in vitro studies to have higher selectivity for the DA transporter. We compared [¹²³I]-CIT and [¹²³I]IPCIT SPET imaging and plasma metabolite analyses in baboons to evaluate the potential advantages of [¹²³I]IPCIT for quantitative in vivo measurements of DA transporter densities. Both tracers had low levels (2% of total plasma¹²³I activity) of lipophilic radiolabeled metabolites at 420 min. [¹²³I]IPCIT had significantly higher binding to plasma proteins. The average percent free (nonprotein bound) [¹²³I]-CIT and [¹²³I]IPCIT were 52%±7% and 14%±6%, respectively. Region of interest uptake data were normalized by injected dose and body weight. Consistent with the high density of 5-HT transporters in the midbrain and the lower 5-HT transporter affinity of IPCIT, the normalized peak specific midbrain uptake of [¹²³I]-CIT (1.7±0.5) was higher than that of [¹²³I]IPCIT (0.4±0.2). Consistent with its greater lipophilicity, [¹²³I]IPCIT had higher nonspecific uptake, such that normalized cerebellar uptake of [¹²³I]IPCIT was about twice that of [¹²³I]-CIT. The ratio of specific to nonspecific uptake in striatum was greater for [¹²³I]-CIT compared to [¹²³I]IPCIT; however, striatal binding potentials and distribution volumes were not significantly different. In conclusion, [¹²³I]IPCIT demonstrated in vivo a higher DA transporter selectivity and higher level of nonspecific uptake.     

Enhancement of [123I]β-CIT binding in the striatum with clomipramine: Is there a serotonin-dopamine interaction?

Many reports support the concept of serotonergic-dopaminergic interaction in the brain. However, at present, there are few methods to study this relationship in vivo. The purpose of this study was to investigate the effect of serotonin (5-HT) uptake inhibitor, clomipramine, on a dopamine (DA) transporter ligand, [¹²³I]-CIT (RTI-55), in rat brain. Dose-dependent changes in [¹²³I]-CIT specific binding induced by clomipramine were studied in the striatum (rich in DA transporter) and the hypothalamus (rich in 5-HT transporter). The changes in the time-activity curves of [¹²³I]-CIT specific binding after clomipramine injection were also examined in these two regions. Using the cerebellum as the reference region,k ₃ andk ₄ values with and without clomipramine administration were estimated by a two-compartment kinetic analysis. Clomipramine inhibited [¹²³I]-CIT specific binding in the hypothalamus, but enhanced its specific binding in the striatum in a dose-dependent manner. Kinetic analysis showed thatk ₃ in the striatum was increased by 55%. In conclusion, enhancement of [¹²³I]-CIT binding in the striatum after clomipramine administration indicated the possibility of 5-HT-DA interaction.     

Differential kinetics of [123I]β-CIT binding to dopamine and serotonin transporters

Iodine-123-labelled 3-(4-iodophenyl)tropane-2-carboxylic acid ([¹²³I]-CIT) labels both the dopamine transporter (DAT) and the serotonin transporter (5-HTT) and this ligand is able to clarify pathological changes in both dopaminergic and serotonergic systems. However, the differential kinetics of -CIT binding to DAT and 5-HTT has not been clarified fully. In this study we examined time-activity curves of [¹²³I]-CIT in individual regions in the rat brain. Using cerebellum as the reference region,k ₃ andk ₄ values were estimated by a two-compartment kinetic analysis. In the striatum, the kinetics was slowest among all brain areas. In this area specific binding reached its peak 4 h after the injection. In the hypothalamus, specific binding reached its peak 1 h after the injection and its amount did not change until 4 h after the injection. In the occipital cortex, the binding and washout of the ligand were fastest among all brain regions. Estimatedk ₃ values were 0.040±0.003 in the striatum, 0.019±0.002 in the hypothalamus and 0.082±0.011 in the occipital cortex (min^–t, mean ±SD). Estimatedk ₄ values were 0.0034±0.0005 in the striatum, 0.0071±0.0009 in the hypothalamus and 0.083±0.013 in the occipital cortex (min^–1, mean ±SD). Therefore binding kinetics of [¹²³I]-CIT in the region rich in DAT is apparently different from that in the region rich in 5-HTT. These results will provide fundamental data to image both DAT and 5-HTT in one series of examinations with [¹²³I]-CIT.     

A new model for separation between brain dopamine and serotonin transporters in <Superscript>123</Superscript>I-β-CIT SPECT measurements: normal values and sex and age dependence

¹²³I--CIT is a radioactive ligand for single-photon emission computed tomography (SPECT) imaging of the pre-synaptic (transporter) re-uptake sites for dopamine (DAT) and serotonin (5HTT), and it is widely used to visualize monoamine turnover. Since ¹²³I--CIT uptake occurs at 5HTT and DAT sites in conjunction with the presence of freely soluble ¹²³I--CIT in brain tissue, adequate separation of these three components is necessary. However, only partial separation is possible with current methods. Two main strategies have previously been used for ¹²³I--CIT component separation, based on the following considerations: (1) the faster uptake rate for 5HTT compared with DAT enables temporal separation by performing 5HTT imaging at 1–2 h and DAT imaging at 20–24 h; (2) blocking the 5HTT re-uptake with citalopram renders ¹²³I--CIT imaging DAT (non-5HTT) specific. In a new analytical model, we combined these two approaches with methods to isolate the passively dissolved ¹²³I--CIT in brain tissue from the monoamine transporter uptake, and to correct the 5HTT and DAT values for concomitant uptake. The new analytical model was used to study brain 5HTT and DAT in 23 normal subjects, with the aim of clarifying the effect of age and sex. A significant correlation between 5HTT and DAT values was found only in the thalamus, indicating successful component separation. Negative correlations between age and DAT were found for basal ganglia, thalami, brain stem and temporal lobes, but not for the frontal, parietal or occipital regions. No correlation with age was found for 5HTT. We found no sex difference for 5HTT or DAT.     

In vitro and in vivo characterisation of nor-β-CIT: a potential radioligand for visualisation of the serotonin transporter in the brain

Radiolabelled 2-Cabomethoxy-3-(4-iodophenyl)tropane (-CIT) has been used in clinical studies for the imaging of dopamine and serotonin transporters with single-photon emission tomography (SPET). 2-Carbomethoxy-3-(4-iodophenyl)nortropane (nor--CIT) is a des-methyl analogue of -CIT, which in vitro has tenfold higher affinity (IC₅₀=0.36 nM) to the serotonin transporter than -CIT (IC₅₀=4.2 nM). Nor--CIT may thus be a useful radioligand for imaging of the serotonin transporter. In the present study iodine-125 and carbon-11 labelled nor--CIT were prepared for in vitro autoradiographic studies on post-mortem human brain cryosections and for in vivo positron emission tomography (PET) studies in Cynomolgus monkeys. Whole hemisphere autoradiography with [¹²⁵I]nor--CIT demonstrated high binding in the striatum, the thalamus and cortical regions of the human brain. Addition of a high concentration (1 M) of citalopram inhibited binding in the thalamus and the neocortex, but not in the striatum. In PET studies with [¹¹C]nor--CIT there was rapid uptake of radioactivity in the monkey brain (6% of injected dose at 15 min) and high accumulation of radioactivity in the striatum, thalamus and neocortex. Thalamus to cerebellum and cortex to cerebellum ratios were 2.5 and 1.8 at 60 min, respectively. The ratios obtained with [¹¹C]nor--CIT were 20%–40% higher than those previously obtained with [¹¹C]-CIT. Radioactivity in the thalamus and the neocortex but not in the striatum was displaceable with citalopram (5 mg/kg). In conclusion, nor--CIT binds to the serotonin transporter in the primate brain in vitro and in vivo and has potential for PET and SPET imaging of the serotonin transporter in human brain.     

The dosimetry of iodine-123 labelled 2β-carbomethoxy-3β-(4-iodophenyl)tropane

This report documents the radiation dosimetry of iodine-123 labelled 2-carbomethoxy-3-(4-iodophenyl)tropane [¹²³I]-CIT in humans. The mean absorbed doses for various organs and the effective dose equivalent were estimated from whole-body scans, blood samples and single-photon emission tomography scans acquired up to 22 h after the injection of a known amount of tracer. The basal ganglia, the liver and the lower large intestinal wall received the highest mean absorbed doses of 0.270 mGy/MBq, 0.038 mGy/MBq and 0.034 mGy/MBq, respectively. The effective dose equivalent for adults was estimated using 11 organs and the ICRP-87 radiation dose model and was 0.031 mSv/MBq. The radiation dose to the basal ganglia limits the maximum injected activity of [¹²³I]-CIT to 185 MBq for a single study.     

Initial experience with single-photon emission tomography using iodine-123-labelled 2 β-carbomethoxy-3β-(4-iodophenyl)tropane in human brain

The iodinated cocaine analogue 2-carbomethoxy-3-(4-iodophenyl)tropane ([¹²³I]-CIT), a new dopamine transporter, was preliminarily tested in human brain. Two normal volunteers and two patients with Parkinson's disease were imaged with a high-resolution single-photon emission tomography scanner. The specific binding of [¹²³I]-CIT in the basal ganglia and thalamus was high in normal volunteers. In addition, there was relatively intense uptake in the medial prefrontal area. Patients with Parkinson's disease who were older than controls showed significantly lower specific binding in the basal ganglia and thalamus and no uptake in the medial prefrontal cortex. This decrease in the dopamine transporter may be age related. Correspondence to: J.T. Kuikka     

Preparation of crystalline bovine liver β-glucuronidase

Summary A method is described for the preparation of pure -glucuronidase from bovine liver. The procedure includes ammonium sulfate, acetone and ethanol fractionation and a simple two-step ion exchange chromatography. The yield is acceptable and the method requires only standard laboratory equipment. The pure enzyme is easily crystallized from ammonium sulfate. Some practical applications of the pure -glucuronidase are discussed.     

β-Methyl-15-p-iodophenylpentadecanoic acid metabolism and kinetics in the isolated rat heart

The use of 15-p-iodophenyl--methyl-pentadecanoic acid (Me-IPPA) as an indicator of long chain fatty acid (LCFA) utilization in nuclear medicine studies was evaluated in the isolated, perfused, working rat heart. Time courses of radioctivity (residue curves) were obtained following bolus injections of both Me-IPPA and its straight chain counterpart 15-p-iodophenyl-pentadecanoic acid (IPPA). IPPA kinetics clearly indicated flow independent impairment of fatty acid oxidation caused by the carnitine palmitoyltransferase I inhibitor 2[5(4-chlorophenyl)pentyl]oxirane-2-carboxylate (POCA). In contrast, Me-IPPA kinetics were insenstive to changes in fatty acid oxidation rate and net utilization of long chain fatty acid. Analysis of radiolabeled species in coronary effluent and heart homogenates showed the methylated fatty acid to be readily incorporated into complex lipids but a poor substrate for oxidation. POCA did not significatly alter metabolism of the tracer, suggesting that the tracer is poorly metabolized beyond Me-IPPA-CoA in the oxidative pathway.     

Cardiac iodine-123 metaiodobenzylguanidine uptake in animals with diabetes mellitus and/or hypertension

The aim of the present study was to evaluate the use of the noradrenaline analogue iodine-123 metaiodobenzylguanidine ([¹²³I]MIBG) for the assessment of cardiac sympathetic activity in the presence of diabetes mellitus and/or hypertension in animal models. One model used Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) rendered diabetic at 12 weeks of age by an intravenous injection of streptozotocin (STZ). The other model used lean and obese Zucker rats. In all groups basic haemodynamic values were established and animals received an intravenous injection of 50 Ci [¹²³I]MIBG. Initial myocardial uptake and washout rates of [¹²³I]MIBG were measured scintigraphically during 4 h. After sacrifice, plasma noradrenaline and left cardiac ventricular -adrenoceptor density was determined. The diabetic state, both in STZ-treated rats (direct induction) and in obese Zucker rats (genetic induction), appeared to induce a lower cardiac density of -adrenoceptors, indicative of increased sympathetic activity. Cardiac [¹²³I]MIBG then showed increased washouts, thereby confirming enhanced noradrenergic activity. This parallism of results led to the conclusion that [¹²³I]MIBG wash-out measurements could provide an excellent tool to assess cardiac sympathetic activity non-invasively. However, in hypertension (WKY vs SHR), both parameters failed to show parallelism: no changes in -adrenoceptor density were found, whereas [¹²³I]MIBG wash-out rate was increased. Thus, either [¹²³I]MIBG washout or ß-adrenoceptor density may not be a reliable parameter under all circumstances to detect changes in the release of noradrenaline. Changes in the initial uptake of [¹²³I]MIBG were observed as well. This may be a good marker for the disappearance of cardiac innervation, but it seems not to be a good parameter for distinguishing between loss of sympathetic innervation and enhanced uptake of noradrenaline in pathological conditions.     

Targeting of<Emphasis Type="Italic"> lacZ</Emphasis> reporter gene expression with radioiodine-labelled phenylethyl-β-<Emphasis Type="SmallCaps">d</Emphasis>-thiogalactopyranoside

There has recently been increasing interest in the development of radioprobes that specifically target proteins transcribed from expression of reporter genes of interest. The purpose of this study was to develop a radioprobe that targets one of the most widely used reporter genes, the bacterial lacZ gene. We synthesised and purified radioiodine-labelled phenylethyl--d-thiogalactopyranoside (PETG), a competitive inhibitor specific against Escherichia coli -galactosidase. We showed that [¹²⁵I]iodo-PETG specifically binds to -galactosidase as verified by column chromatography and polyacrylamide gel electrophoresis after incubation of radiotracer with the protein. We also showed through enzyme kinetic studies that iodo-PETG retains inhibitory action against -galactosidase activity. COS-7 cells infected with a recombinant adenovirus expressing the lacZ gene had viral titre-dependent enhancements in [¹²⁵I]iodo-PETG uptake (r²=0.897; P=0.001), which reached up to 642.5%±16.7% of control levels (P<0.00001). Moreover, the level of uptake was highly correlated to luminescent measurements of -galactosidase activity (r²=0.878; P<0.0001). These results confirm that radioiodine-labelled PETG specifically targets -galactosidase and that its uptake rates faithfully reflect levels of expression of the lacZ reporter gene. Further investigations were performed in nude mice bearing human neuroblastoma tumours transferred with the lacZ gene. Compared with control tumours, lacZ-expressing tumours were slightly better visualised on [¹²³I]iodo-PETG images and had a modest increase in tumour to muscle count ratio (2.6±0.2 vs 1.9±0.1, P<0.05). The present results provide proof-of-principle for the potential of radiolabelled inhibitors as promising radiotracers to monitor lacZ gene expression levels. Future modifications to improve cell permeability should enhance in vivo contrast levels and may allow the use of radiolabelled -galactosidase inhibitors for non-invasive monitoring of lacZ gene expression.This work was presented in part at the 49th Annual Meeting of the Society of Nuclear Medicine, LA, USA, June 15–19, 2002.     

Characterization of IMPY as a potential imaging agent for β-amyloid plaques in double transgenic PSAPP mice

Deposition of -amyloid (A) plaques in the brain is likely linked to the pathogenesis of Alzheimers disease (AD). Developing specific A aggregate-binding ligands as in vivo imaging agents may be useful for diagnosis and monitoring the progression of AD. We have prepared a thioflavin derivative, 6-iodo-2-(4-dimethylamino-)phenyl-imidazo[1,2-a]pyridine, IMPY, which is readily radiolabeled with ¹²⁵I/¹²³I for binding or single-photon emission computerized tomography (SPECT) imaging studies. Characterization of [¹²⁵I]IMPY binding to plaque-like structures was evaluated in double transgenic PSAPP mice. [¹²⁵I]IMPY labeled A plaques in transgenic mouse brain sections, and the labeling was consistent with fluorescent staining and A-specific antibody labeling. Significant amounts of A plaques present in the cortical, hippocampal, and entorhinal regions of the transgenic mouse brain were clearly detected with [¹²⁵I]IMPY via ex vivo autoradiography. In contrast, [¹²⁵I]IMPY showed little labeling in the age-matched control mouse brain. Tissue homogenate binding further corroborated the A plaque-specific distribution in various brain regions of transgenic mouse, and correlated well with the known density of A deposition. Using a tissue dissection technique, [¹²⁵I]IMPY showed a moderate increase in the cortical region of transgenic mice as compared to the age-matched controls. In vitro blocking of [¹²⁵I]IMPY by carrier observed via autoradiography in mouse brain sections was not replicated by an in vivo blocking experiment in living TT mouse brain. The failure was most likely due to a significant carrier effect, which slows down the tracer in vivo metabolism, leading to an increased brain uptake. Taken together, these data indicate that [¹²³I]IMPY is a potentially useful SPECT imaging agent for in vivo labeling of A plaques in the living brain.     

PET imaging of brain with the β-amyloid probe, [11C]6-OH-BTA-1, in a transgenic mouse model of Alzheimer’s disease

Purpose The purpose of this study was to evaluate the capacity of [¹¹C]6-OH-BTA-1 and positron emission tomography (PET) to quantify -amyloid (A) plaques in the Tg2576 mouse model of Alzheimers disease (AD).Methods PET imaging was performed with the NIH ATLAS small animal scanner in six elderly transgenic mice (Tg2576; age 22.0±1.8 months; 23.6±2.6 g) overexpressing a mutated form of human -amyloid precursor protein (APP) known to result in the production of A plaques, and in six elderly wild-type litter mates (age 21.8±1.6 months; 29.5±4.7 g). Dynamic PET scans were performed for 30 min in each mouse under 1% isoflurane inhalation anesthesia after a bolus injection of 13–46 MBq of [¹¹C]6-OH-BTA-1. PET data were reconstructed with 3D OSEM. On the coronal PET image, irregular regions of interest (ROIs) were placed on frontal cortex (FR), parietal cortex (PA), striatum (ST), thalamus (TH), pons (PO), and cerebellum (CE), guided by a mouse stereotaxic atlas. Time–activity curves (TACs) (expressed as percent injected dose per gram normalized to body weight: % ID-kg/g) were obtained for FR, PA, ST, TH, PO, and CE. ROI-to-CE radioactivity ratios were also calculated. Following PET scans, sections of mouse brain prepared from anesthetized and fixative-perfused mice were stained with thioflavin-S.Results TACs for [¹¹C]6-OH-BTA-1 in all ROIs peaked early (at 30–55 s), with radioactivity washing out quickly thereafter in both transgenic and wild-type mice. Peak uptake in all regions was significantly lower in transgenic mice than in wild-type mice. During the later part of the washout phase (12–30 min), the mean FR/CE and PA/CE ratios were higher in transgenic than in wild-type mice (1.06±0.04 vs 0.98±0.07, p=0.04; 1.06±0.09 vs 0.93±0.08 p=0.02) while ST/CE, TH/CE, and PO/CE ratios were not. Ex vivo staining revealed widespread A plaques in cortex, but not in cerebellum of transgenic mice or in any brain regions of wild-type mice.Conclusion Marked reductions in brain uptake of this radioligand in transgenic mice may be due to reduced cerebral blood flow relative to that in wild-type mice. Specific [¹¹C]6-OH-BTA-1 binding to A plaques, if any, is probably very low, as reflected in the small FR/CE and PA/CE ratio differences. FR/CE and PA/CE ratios are considerably higher in AD patients while A plaque densities in 22-month-old transgenic mice may be expected to show essentially the same density as is observed in the AD brain. This implies that the absence of tracer retention in 22-month-old transgenic mice may be due to the smaller number of A plaque binding sites and/or to lower affinity of the binding sites for [¹¹C]6-OH-BTA-1 as compared with AD patients. [¹¹C]6-OH-BTA-1 shows excellent brain uptake in mice.This work was presented at the 51st Annual Meeting of the Society of Nuclear Medicine in Philadelphia, PA, June 19–23, 2004.     

“Menigeal sign”: a characteristic finding of meningiomas on contrast-enhanced MR images

Summary In meningiomas, a flat, contrast-enhancing, probably dural structure adjacent to the tumor can occasionally be observed on Gadolinium-DTPA enhanced MR images. This so called meningeal sign was evaluated with respect to the differential diagnosis of meningiomas in MR imaging. The study included 29 patients with intracranial meningiomas and 24 patients with non-meningeal brain tumors. In all meningiomas, MR studies included T2-weighted as well as unenhanced and Gadolinium-DTPA-enhanced T1-weighted images. In all nonmeningeal tumors, Gd-DTPA-enhanced MR images were available. All images were evaluated with respect to the presence of the meningeal sign. In meningiomas, a meningeal sign was seen in 15/29 cases on Gadolinium-DTPA-enhanced images. No abnormalities corresponding to the areas of contrast enhancement were found on unenhanced T2- and T1-weighted MR images. In nonmeningeal tumors only 2/24 cases showed a meningeal sign. In conclusion, with a sensitivity of 52% and a specificity of 92%, the demonstration of the meningeal sign improved the differential diagnosis of intracranial meningiomas in contrast-enhanced MR imaging.     

Use of iodine-123 metaiodobenzylguanidine myocardial imaging to predict the effectiveness of β-blocker therapy in patients with dilated cardiomyopathy

It is crucial to predict drug effectiveness in chronic disease, such as dilated cardiomyopathy (DCM), in which the left ventricular (LV) function might be improved by -blocker therapy. As the functional improvement effected by -blocker therapy takes more than 2 months, we investigated whether iodine-123 metaiodobenzylguanidine (¹²³I-MIBG) imaging could be used to predict drug effectiveness. We studied 13 patients (11 men and two women; mean age, 43±13 years) with DCM and seven normal subjects (six men and one woman; mean age, 48±16 years). We obtained myocardial single-photon emission tomography (SPET) images 15 min and 4 h after administration of¹²³I-MIBG (111 MBq). Studies were performed in the patients with DCM before and 1 and 3 months after the administration of metoprolol and in the normal subjects. We calculated the regional¹²³I-MIBG washout rate (r-WR) in the SPET image, and the global¹²³I-MIBG washout rate (g-WR) and heart-mediastinum activity ratio (H/M) using the anterior planar image. We classified patients into those showing a 5% increase in LV ejection fraction (LVEF) at 3 months compared with LVEF values before the treatment (group 1,n=7) and those showing a <5% increase in LVEF (group 11,n=6). In group I, the r-WR values at pretreatment and at 1 month and 3 months of treatment, respectively, were 36%±19%, 29%±14%* and 25%±13%* in the anterior segment, 39%±17%, 33%±17%** and 28%±17%* in the lateral segment, 36%±16%, 31%±14%* and 22%±12%** in the septal segment and 40%±11%, 37%±19% and 31%±18%* in the inferior segment; the g-WR was 45%±11%, 43%±10% and 34%±9%^*, respectively (*P<0.05, **P<0.01 vs pretreatment). In group II, there were no significant changes in regional or global parameters during the 3-month period. In normal subjects, the r-WR values in each of the anterior, lateral, septal and inferior segments were significantly lower than those in groups I and II. These values were 18%±9%, 18%±15%, 20%±12% and 21%±15%, respectively. This study demonstrated that with regional assessment¹²³I-MIBG SPET imaging can be used to predict the functional improvement of LVEF at 1 month of -blocker therapy in patients with DCM.     

Dopamine transporter SPECT using fast kinetic ligands: <Superscript>123</Superscript>I-FP-β-CIT versus <Superscript>99m</Superscript>Tc-TRODAT-1

A comparative study was carried out on two promising presynaptic dopamine transporter single-photon emission tomography (SPECT) radioligands with a fast pharmacokinetic profile, ¹²³I-FP--CIT (FP) and ^99mTc-TRODAT-1 (TR), in order to assess their differential diagnostic power in early parkinsonism and their sensitivity for detection of disease progression. This cross-sectional study was conducted on 96 patients with early-stage parkinsonism referred in a tertiary clinical setting. Mean disease duration was 2.0±1.3 years, and patients had a modified Hoehn and Yahr (H&Y) stage of 1–2 (average 1.2). Forty-seven patients received TR, and 49 received FP. In both groups, ten patients with normal presynaptic function were included as a control population; all other patients were clinically diagnosed as having idiopathic Parkinsons disease. Groups were matched for gender, age, disease duration and modified H&Y stage. Triple-head gamma camera SPECT was analysed using a semiquantitative index of transporter binding (BI). Discriminant analysis with cross-validation resulted in a maximal classification accuracy for FP of 93% (sensitivity 95% and specificity 86%) for the contralateral putamen BI. For TR, the corresponding values were 87% accuracy, 92% sensitivity and 70% specificity. For FP, disease duration was correlated with both the putamen BI (–8.8%/year, =–0.41, P=0.025) and the putamen/caudate ratio (–7.4%/year, =–0.51, P=0.004), but for TR no significant correlation was found (all P values >0.5). In conclusion, both FP and TR show high sensitivity in a clinically relevant setting, but FP has superior accuracy for early differential diagnosis of idiopathic parkinsonism and non-degenerative extrapyramidal disorders, as well as better sensitivity for disease follow-up.     

Die besonderen konstruktionsmerkmale des japanischen „Tan-to“-(Messers) als Kriterien für dessen Gefährlichkeit

Zusammenfassung Es wird auf die besondere Klingenform japanischer Blankwaffen und auf die Neuentwicklung eines Verwandlungs-Tan-to verwiesen. Bei letzterem läßt sich die Klinge in der Handgriffmitte um 90° drehen und arretieren, eine ideale Fixierung dieses Messers durch Faustschluß am Quergriff. Durch diese Bedingungen ist eine hohe Verletzungsgefährdung mit tödlichem Ausgang gegeben. Diese seit kurzer Zeit im Handel erhältlichen Messer sollten nach § 37 Waff G umgehend als verbotene Gegenstände definiert werden.     

Early-stage [123I]β-CIT SPECT and long-term clinical follow-up in patients with an initial diagnosis of Parkinson’s disease

Purpose Previous studies using dopamine transporter single-photon emission computed tomography (SPECT) to try and distinguish between patients with idiopathic Parkinsons disease (IPD) and patients with atypical parkinsonian syndromes (APS) have mainly focussed on patients with an already established clinical diagnosis of several years duration. Differences in the pattern of striatal involvement between IPD and APS have been found in only few studies. We hypothesized that distinguishing SPECT features might be most pronounced at an early disease stage, and the purpose of the present study was to investigate this hypothesis.Methods The study included 72 patients with an initial clinical diagnosis of IPD, supported by decreased striatal [¹²³I]-CIT binding on baseline SPECT. In ten patients, the diagnosis was changed to APS over a mean follow-up period of 62 months. We retrospectively compared the patterns of striatal involvement on the baseline SPECT scans between the group of patients (re)diagnosed with APS and the remaining 62 patients in whom a diagnosis of IPD was maintained.Results In the group of patients with APS, baseline [¹²³I]-CIT binding in both caudate nuclei was lower than in the group of patients with IPD. In addition, putamen to caudate binding ratios were higher in the group of APS patients. In spite of these differences, individual binding values showed considerable overlap between the groups.Conclusion [¹²³I]-CIT SPECT scanning in early-stage, untreated parkinsonian patients revealed a relative sparing of the caudate nucleus in patients with IPD as compared to patients later (re)diagnosed with APS. Nevertheless, the pattern of striatal involvement appears to have little predictive value for a later re-diagnosis of APS in individual cases.     

Thyroid abnormality secondary to tortous carotid artery

A 59-year-old man was referred to the nuclear medicine service for a thyroid scan, as his neck was thick and the thyroid was not palpable. In the past the patient had undergone head and neck irradiation for acne. A¹²³I-thyroid scan was interpreted as a cold nodule in the lower pole of the right lobe, but thyroid ultrasound showed no thyroid abnormality. Repeat ultrasound examination eventually showed a tortuous carotid artery behind the lower pole of the right lobe of the thyroid that corresponded to the cold defect.