A. Bossuyt

99Tcm-DMSA renal scintigraphy for acute pyelonephritis in adults : Planar and/or SPET imaging ?

A number of authors have indicated a more sensitive detection of renal cortical defects using single photon emission tomography (SPET) compared with planar imaging when performing 99Tcm-dimer-captosuccinic acid (99Tcm-DMSA) renal scintigraphy. The place of SPET in the evaluation of kidneys in adults suspected of acute pyelonephritis (APN) remains controversial, however. The aim of this study was to address the role of SPET in adult patients suspected of having APN. Planar and SPET 99Tcm-DMSA renal imaging was performed in 53 patients. The data sets were separated and presented in random order to three independent observers. The kidneys were divided into three segments, which were classified as normal, definitely abnormal or equivocal. Ir. a second step, the number of lesions (definite or equivocal) on planar and SPET imaging were counted. The overall concordance between the planar and SPET imaging scores was 90.9, 89.9 and 87.7% for the three observers, respectively. Inter-observer discordance was recorded in a small percentage of both planar and SPET images. The number of lesions, based on the average of the three observers, was 22 for planar and 25 for SPET imaging. Obvious differences between observers were noted. The planar images were more often interpreted as equivocal by the least experienced observer. The more experienced observers gained limited additional information using SPET routinely. Most equivocal lesions on the planar scintigrams were observed in the lower segment. For SPET, no such distribution was noted. High-quality 99Tcm-DMSA images allow the detection of the same number of lesions as SPET in adults suspected of APN.

Initial clinical experience with a new kit formulation of Tc-99m-β galactosylated albumin for functional hepatic imaging

We studied the biodistribution, imaging characteristics and pharmacokinetics of a new kit formulation of Tc-99m-β galactosylated albumin (NGA). In all subjects, even in those patients with severe hepatocellular dysfunction, Tc99m-NGA provided excellent hepatic images and the liver was the only site of uptake of the tracer. Between 2 and 15 min post injection, the blood disappearance curve was found to be adequately described by a mono-exponential function. The fractional desappearance rate (ki) ranged from 0.089 min-1 in normals to 0.039 in cirrhotic patients. The initial volume of distribution (VDi) of the tracer was always higher than the expected blood volume, the difference ranging from 5% in patients with the most impaired liver function to 54% in those with normal liver function. Both parameters discriminated completely the cirrhotic patients from the normal control group. A significant dose dependency of VDi was observed indicating that at least during the minutes after injection liver uptake is determined by both available receptor concentration and hepatic blood flow.

Reduced left subgenual anterior cingulate cortical activity during withdrawal-related emotions in melancholic depressed female patients

BACKGROUND Research regarding the neurocircuitry in mood disorders suggests an important role for affective information processing of the subgenual part of the anterior cingulate cortex (Cg25: Brodmann area 25). OBJECTIVE In this study, we focused on Cg25 neuronal responses in depressed females using a paradigm in which emotions are elicited without explicit cognitive control, relying on the salient nature of the mood inducing stimuli eliciting approach-related emotions (like happiness) or withdrawal-related emotions (like disgust). METHODS Twelve treatment-resistant melancholic depressed women and 12 healthy female control subjects were asked to passively view blocks of emotionally valenced baby faces while undergoing functional magnetic resonance imaging (fMRI). RESULTS Compared to the healthy females, the depressed patients displayed significantly higher bilateral Cg25 neuronal activities in both emotional conditions. In melancholically depressed women, we found significantly less left-sided than right-sided Cg25 neuronal activity during the withdrawal-related emotions, while right-sided Cg25 activity was comparable for both emotional responses. CONCLUSIONS Our results indicate that in depressed women the left Cg25 modulates intense visceral emotional responses to aversive visual stimuli. This could help explain why the left Cg25 provides a valid target region for antidepressant treatment strategies in unipolar melancholic depression.

Regional distribution of 123I-(ortho-iodophenyl)-pentadecanoic acid and 99Tcm-MIBI in relation to wall motion after thrombolysis for acute myocardial infarction

To characterize the myocardium after thrombolytic therapy for infarction single photon emission computed tomographic (SPECT) studies with 123I-(ortho-iodophenyl)-pentadecanoic acid (oPPA) and 99Tcm-methoxyisobutyl isonitrile (MIBI) were obtained at rest in nine patients within a fortnight after the acute event. A decreased oPPA activity compared to MIBI was observed in 15/45 segments (7/9 patients). The segments with discordant oPPA/MIBI activities showed less severe wall motion abnormalities than the segments with concordant decreased oPPA and MIBI activities (P=0.004). A significant association was found between discordant oPPA/MIBI activities and the early evolution of wall motion following thrombolysis: discordant oPPA/MIBI activities were present in nine of the 11 segments (82%) with improved wall motion, while the wall motion of the seven segments with similar decreased oPPA and MIBI activities was unchanged or had deteriorated (P=0.018). It is concluded that metabolic abnormalities often persist longer than perfusion and wall motion abnormalities soon after thrombolysis, and that 123I-oPPA in combination with 99Tcm-MIBI is useful to demonstrate myocardial areas which have been salvaged by thrombolysis.

Quantification of 99Tcm-HMPAO brain SPET in two series of healthy volunteers using different triple-headed SPET configurations : Normal databases and methodological considerations

We evaluated the methodological issues underlying the assessment of normal confidence intervals, as used in clinically based region-of-interest (ROI) semi-quantification of 99Tcm-HMPAO brain SPET. At two different centres equipped with high-resolution, triple-headed gamma cameras, HMPAO SPET scans were performed on two groups of 24 and 15 healthy volunteers respectively. Together with an operator-defined analysis (ODA), a semi-automated analysis (SAA) was conducted on the normal datasets in one centre. Tests of intra- and inter-observer variability were performed. Repeat scans were performed within 72 h after the first to analyse short-term regional inter-study variations. The overall regional uptake showed significant differences in most regions between both normal datasets. Intra-observer and inter-observer reproducibility were on average within 4% for the ODA, while for the SAA it was less than 1%. Inter-study variations were excellent for both centres, ranging from -4% to +3% for most regions studied. The variability in clinical brain perfusion studies largely depends on the reproducibility of the data analysis technique. A semi-automated approach shows clear advantages over an entirely operator-defined approach. Intra-subject repeat studies show enough stability for use as reliable baseline measurements in the construction of a normal database or to allow activation studies with high sensitivity.

Fascial Tc-99m MDP uptake in eosinophilic fasciitis as demonstrated by SPECT.

BACKGROUND The presence of bone-seeking radiopharmaceutical uptake in extraskeletal tissues of the lower or upper extremities may indirectly reflect the presence of active inflammatory lesions in patients in whom systemic disease is suspected. MATERIALS AND METHODS The authors present the case of a 26-year-old woman who had mixed signs of scleroderma and cosinophilic fasciitis, in whom misleading findings on planar bone scintigraphy suggested diffuse muscular tracer uptake in the lower extremities. RESULTS However, using additional SPECT imaging of the pelvis and thighs, it was shown that the soft tissue radioactivity was clearly restricted to the fascia overlying the muscles. The fascial localization of the inflammation was confirmed by biopsy. CONCLUSION SPECT imaging was proven useful in indicating the exact localization of an active inflammatory process in the muscle fascia.

Uptake of In-111 antifibrin in crush injuries.

In-111 labeled antifibrin antibodies have been put forward for the detection of deep venous thrombi in man. They bind specifically to human fibrin, which is present in fresh as well as aged thrombl. However, the presence of this protein, which results from fibrinogenolysis, is not limited to clots. The authors report on a patient suffering from crush syndrome and suspected of having deep venous thrombosis, in whom extravascular uptake of in-111 antifibrin was observed in a thigh hematoma. No deep venous thrombosis could be demonstrated.

Fast, low-temperature preparation of carrier-free 17-123I-heptadecanoic acid applied for liver and heart scintigraphy

A high-yield method for labelling 17-I-heptadecanoic acid with 123I is described, and a clinical evaluation of the radiopharmaceutical is given. The labelling procedure is based on the use of a conventional ultrasonic bath. It was found that the addition of thiosulphate to the reaction medium avoids the formation of labelled side products and increases the yield considerably. The carrier-free 17-123I-heptadecanoic acid (2 mCi) in 6% human serum albumin was injected IV for heart and liver studies on selected patients with cirrhosis (alcohlic, post-necrotic) and diabetes.

P02-08 - The influence of treatment-resistance on the serotonin 2A receptor in unipolar melancholic depression

Introduction Major depression is one of the most common mental diseases, and quite a number of patients are resistant to several psychopharmacological interventions, even when applying current treatment guidelines. To date, it remains unclear as to how the serotonergic system is implicated in treatment-resistance found in melancholically depressed patients. Objectives & aims In this study, we examined the involvement of post-synaptic 5-HT2A receptors in the pathophysiology of treatment resistance in major depression with 123I-5-I-R91150 SPECT, focusing on the frontal cortex and hippocampus. Method 15 unipolar antidepressant naive (ADN) patients and 15 treatment-resistant depressed (TRD) patients, all of the melancholic subtype, matched for age and gender were studied. All subjects were antidepressant free when they underwent a static 123I-5-I-R91150 SPECT scan. Results Compared to ADN patients, TRD patients displayed significantly less 5-HT2A receptor binding index (BI) in the dorsal regions of the prefrontal cortex and in the anterior cingulate cortex. No hippocampal 5-HT2A receptor BI differences were observed. Conclusions Our results suggest that when confronted with treatment resistance in melancholic depression the 5-HT2A receptors in the DPFC-ACC axis are significantly more down-regulated when compared to depressed ADN patients. This might to some extent explain the observed continued cognitive problems and might reflect the long-term serotonin depletion with reduced neurogenesis in treatment resistant patients.

P.2.b.024 The influence of treatment-resistance on the serotonin 2A receptor in unipolar melancholic depression

It has been previously showed by microdialysis studies that rat cortical serotonin (5-HT) levels significantly increases following single subcutaneous trazodone administration (3 and 10mg/kg) [1]. Aim of the present study is to assess the potential involvement of alpha2-adrenoceptors in the trazodone-induced 5-HT cortical increase. Trazodone interaction with alpha2-adrenoceptors was studied in vitro by radioligand technique, while in vivo activity was assessed in freely moving rats using microdialysis coupled with HPLC detection method. Radioligand binding studies on human alpha2adrenoceptors were performed on human recombinant CHO cells. Functional activity was determined by using recombinant CHO or HEK293 cells expressing alpha2-adrenoceptors by means of impedance changes measured by cellular dielectric spectroscopy or cAMP measurement. Microdialysis studies were performed in male adult Wistar rats. All animal-use procedures conformed to the guidelines of the European Community’s Council for Animal Experiments. Rats were anaesthetised and placed in a Kopf stereotaxic frame in order to implant a guide cannula in the frontal cortex (AP 2.7mm, L −1mm, H −1.2mm from the bregma). 5-HT levels were measured following a single subcutaneous administration of trazodone (3, 10mg/kg) and venlafaxine (3, 10mg/kg) or sertraline (10mg/kg) which were used as reference drugs. In order to evaluate the role of alpha2-adrenoceptor, trazodone was administered in rats pretreated with the selective norepinephrine (NE) uptake inhibitor reboxetine (200mg/kg, iv). Moreover, to assess the receptor subtype involved, prazosin (300mg/kg, iv) or yohimbine (100mg/kg, iv), alpha1 and alpha2 antagonist respectively, was administered before reboxetine and trazodone. Binding studies showed that trazodone has high affinity for human alpha2-adrenoceptors. In addition, in vitro functional studies demonstrated antagonistic activity yielding an IC50 of 4.6mM (alpha2A), 10mM (alpha2B) or 11mM (alpha2C). In vivo experiments confirmed that a single subcutaneous administration of trazodone significantly increases cortical 5-HT levels in rats. In the same experimental conditions, the 5-HT and NE reuptake inhibitor venlafaxine and the selective 5-HT uptake inhibitor sertraline did not induce any 5-HT level change. In rats pretreated with reboxetine, trazodone-induced 5-HT increase resulted completely abolished suggesting the involvement of alpha receptors in the effect exerted by trazodone. Temporary blockade of the alpha2-adrenoceptor by yohimbine prevented reboxetine effect and restored trazodone ability to increase 5-HT levels. On the other hand, blockade of the alpha1-adrenoceptor by prazosin was not able to restore trazodone activity. It is worth noting that, in the experimental conditions used, no 5-HT cortical level changes were observed following administration of reboxetine, yohimbine or prazosin alone at the tested doses. The present results provide evidence for alpha2-adrenoceptors involvement in the trazodone modulatory effect of 5-HT cortical levels. The present experimental set, taking into account the effects demonstrated with the well known antidepressant venlafaxine and sertraline, suggests the interaction with the alpha2-adrenoceptors as a possible molecular mechanism for the early onset of trazodone activity.