Peter Blanckaert

Estimates of regional cerebral blood flow and 5-HT2A receptor density in impulsive, aggressive dogs with 99mTc-ECD and 123I-5-I-R91150

Impulsive aggression in dogs has an important impact on human public health. Better insight into the pathophysiology of this phenomenon could lead to more adequate diagnosis and treatment. Indirect in vivo research on peripheral body fluids and post-mortem studies in impulsive animals and humans indicate a deficient serotonergic system in general and disturbances in the serotonin-2A (5-HT2A) receptor in particular. In this study, brain perfusion and the 5-HT2A receptors were examined in impulsive, aggressive dogs, in comparison with a group of normally behaving animals. In order to decide which dogs to include in this study, owners were asked to describe the general behaviour of the dogs, the circumstances in which aggression occurred and their conduct during aggressive acts. Finally, 19 dogs were retained for this study, showing, according to different behavioural specialists, disinhibited dominance aggression. Functional imaging studies were performed on all these dogs. Single-photon emission tomography (SPET) was used to measure regional brain perfusion using technetium-99m labelled ethyl cysteinate dimer (ECD). The 5-HT2A receptor binding properties were investigated using the selective radioligand iodine-123 labelled 5-I-R91150. A significant increase in uptake of the 5-HT2A radioligand was noted in all cortical areas. No significant alterations were found in regional cortical perfusion, indicating that the increased binding index was not a consequence of increased tracer delivery. This study supports a role for the serotonergic system in canine impulsive aggression.

The impact of HF-rTMS treatment on serotonin2A receptors in unipolar melancholic depression

BACKGROUND Currently, the underlying neurobiological mechanism as to how repetitive transcranial magnetic stimulation (rTMS) can alter depressive states remains unclear. Animal data suggest that its influence could occur at the neurotransmitter level, such as modulation of the serotonin system. METHODS Twenty-one antidepressant-free medication-resistant unipolar depressed patients, and 21 age- and gender-matched healthy subjects were studied. We examined the neurobiologic impact of 10 high-frequent (HF)-rTMS sessions applied to the left dorsolateral prefrontal cortex (DLPFC) on postsynaptic 5-HT(2A) receptor binding indices (BI) measured with ¹²³I-5-I-R91150 single photon emission computed tomography (SPECT) only in patients. RESULTS Compared with the control group, patients displayed significantly less bilateral dorsolateral prefrontal cortical and significantly higher left hippocampal baseline 5-HT(2A) receptor BI. Successful HF-rTMS treatment correlated positively with 5-HT(2A) receptor BI in the DLPFC bilaterally and correlated negatively with right hippocampal 5-HT(2A) receptor uptake values. CONCLUSIONS Our results indicate that HF-rTMS treatment affect the serotonergic system. Our data also suggest that this kind of treatment affects 5-HT(2A) receptor BI in the DLPFC and in the hippocampus in different ways.

Tissue perfusion in pathologies of the pancreas: assessment using 128-slice computed tomography

PurposePerfusion CT can provide information regarding blood perfusion and permeability in (tumor) tissues in a non-invasive manner. In this study, values of CT perfusion parameters in several pancreas pathologies were determined and compared to a control population.Materials and methodsDynamic 128-slice perfusion CT was performed in patients admitted to the radiology department between June 2010 and March 2011. Included pathologies were pancreatic adenocarcinoma, acute and chronic pancreatitis, neuroendocrine tumors, and (pseudo)cystic lesions. Parametric mappings of blood flow, blood volume, and permeability surface area product were generated.ResultsBlood flow and blood volume were significantly lower in acute and chronic pancreatitis compared to the control group. In the center of adenocarcinoma tumors, low blood flow and blood volume was observed, gradually increasing toward the tumor rim; perfusion values in pancreatic parenchyma adjacent to the tumor were not significantly different from the control population. In neuroendocrine tumors, significantly increased perfusion values were observed.ConclusionCompared to the control population, significant decreases in perfusion values were observed in all pancreatic pathologies under study, except in neuroendocrine tumors. Perfusion CT values can be used as an additional parameter to differentiate pancreatic pathologies.

Assessment of tumor vascularization in pancreatic adenocarcinoma using 128-slice perfusion computed tomography imaging.

Objective: Computed tomography (CT) perfusion studies can provide valuable information regarding tumor vascularization. We report on a study assessing CT perfusion characteristics in the normal pancreas and in patients with pancreatic adenocarcinoma. Methods: Twenty healthy subjects and 20 patients with histologically confirmed pancreatic adenocarcinoma were included in the study after written informed consent and approval by our institutional review board. All subjects underwent perfusion CT imaging of the pancreas using 128-slice dual-source CT. The scanning sequence included 18 scans. Parametric maps of blood volume (BV), blood flow (BF), and permeability surface area product (PS) were generated and compared with density measurements. Results: In normal pancreas, no significant difference in perfusion values was observed between head, body, and tail of the pancreas. Mean organ values were 76.76 (SD, 15.6) mL/100 g/min, 15.80 (SD, 2.40) mL/100 g, and 27.74 (SD, 16.8) mL/100 g/min for BF, BV, and PS, respectively. Compared with the normal pancreas, a 60% reduction in BF and BV was observed in the tumor tissue. Perfusion values gradually increased toward the tumor rim. Necrotic tumor areas were identified in 25% of patients. No significant differences were observed when comparing normal pancreas and healthy pancreatic tissue in adenocarcinoma patients. Conclusions: The feasibility of whole-tumor perfusion imaging using 128-slice CT was demonstrated in patients with pancreatic adenocarcinoma. Perfusion CT provides additional information compared with image assessment based on density measurements (Hounsfield units) and allows noninvasive assessment of vascularization in the tumor tissue.

In vitro and In vivo Targeting Properties of Iodine-123- or Iodine-131–Labeled Monoclonal Antibody 14C5 in a Non–Small Cell Lung Cancer and Colon Carcinoma Model

Purpose: The monoclonal antibody (mAb) 14C5 is a murine IgG1 directed against a yet undefined molecule involved in cell substrate adhesion found on the surface of malignant breast cancer tissue. mAb 14C5 is able to inhibit cell substrate adhesion and invasion of breast cancer cells in vitro. In normal tissues as well as in the stroma surrounding in situ carcinomas of the breast, no expression of the antigen 14C5 occurs. The aim of this study was to investigate the in vitro and in vivo targeting properties of 123I- and 131I-labeled mAb 14C5 as a novel agent for radioimmunodetection and radioimmunotherapy. Experimental Design: Internalization of mAb 14C5 was investigated with 125I-labeled mAb 14C5 and by confocal laser scanning microscopy. Biodistribution studies of 131I-labeled mAb 14C5 and planar gamma imaging were done in nude mice bearing an A549 (non–small cell lung carcinoma) or a LoVo (colon carcinoma) tumor. Results: Internalization studies with both A549 and LoVo cells showed that 125I-labeled mAb 14C5 is slowly internalized with ∼30% of the initially bound mAb 14C5 internalized after 2 hours at 37°C. Internalization of mAb 14C5 could be visualized with confocal laser scanning microscopy. In vivo, radioisotope uptake peaked at 24 hours for both tumor models (n = 5) with no significant difference in percentage of injected dose/g tissue (A549 10.4 ± 0.8 and LoVo 9.3 ± 0.8). Via planar gamma camera imaging, A549 lung tumors as well as LoVo colon tumors could be clearly visualized. Conclusions: The in vitro and in vivo targeting properties of 123I- and 131I-labeled mAb 14C5 are promising and could provide a new antibody-based agent for radioimmunodetection and radioimmunotherapy of patients bearing antigen 14C5–expressing tumors.

Radiosynthesis, in vitro and in vivo evaluation of 123I-labeled anandamide analogues for mapping brain FAAH.

Fatty acid amide hydrolase (FAAH) is one of the main enzymes responsible for terminating the signaling of endocannabinoids, including anandamide. This paper is the first report of the synthesis, [123I]-labeling and in vitro and in vivo evaluation of anandamide analogues as potential metabolic trapping radioligands for in vivo evaluation of brain FAAH. N-(2-iodoethyl)linoleoylamide (2) and N-(2-iodoethyl)arachidonylamide (4) were synthesized with good yields (75% and 86%, respectively) in a two steps procedure starting from their respective acids. In vitro analyses, performed using recombinant rat FAAH and [3H]-anandamide, demonstrated interaction of 2 and 4 with FAAH (IC50 values of 5.78 microM and 3.14 microM, respectively). [123I]-2 and [123I]-4 were synthesized with radiochemical yields of 21% and 12%, respectively, and radiochemical purities were > 90%. Biodistribution studies in mice demonstrated brain uptake for both tracers (maximum values of 1.23%ID/g at 3 min pi for [123I]-2 and 0.58%ID/g at 10 min pi for [123I]-4). However, stability studies demonstrated the sensitivity of both tracers to dehalogenation.

Variability of CT Contrast Enhancement in the Pancreas: A Cause for Concern?

Background: Multidetector CT is a valuable technique for diagnosis/staging in several pancreatic pathologies. Diagnosis is usually based on tissue density measurements. Recently, newer functional CT techniques have been introduced. The aim of this study was to assess variability in perfusion and dual-energy CT data, and to compare these data with density measurements in the pancreas of a healthy population. Methods: Two groups were included: 20 patients underwent perfusion CT imaging, and 10 patients were scanned using a dual-energy protocol. In both groups, tissue density [Hounsfield units (HU)] was measured in the pancreatic head, body and tail. Functional data were calculated (blood flow/blood volume in the perfusion CT group, iodine concentration in the dual-energy group), and variability was assessed. Results: Density measurements were comparable for the perfusion and dual-energy CT groups, and ranged from 14 to 60 HU. Maximal enhancement differences between the head/body/tail of the pancreas ranged between 2 and 21 HU. Considerable variability was observed, both in density measurements (ranging from 3 to 34%) and in functional parameters (mean variability in perfusion CT parameters blood flow and blood volume was 21.3 and 10% respectively; mean variability in dual-energy iodine-mapping results was 24.4%). Conclusion: This study demonstrated the presence of important intraindividual variability in pancreatic tissue contrast enhancement, regardless of the CT technique used. Considering the variability observed in this study, the use of cut-off values to characterize pancreatic pathologies seems troublesome, and morphologic primary and secondary changes will remain important, even when using novel functional imaging techniques.

Treatment for substance use disorders: the Belgian Treatment Demand Indicator registration protocol.

BackgroundRegistration of patients with substance use disorders is of key importance to get insights and to study trends in patients characteristics and substance use patterns. The Treatment Demand Indicator (TDI) is gathering this information at European level since 2000. In Belgium, this registration started at national level in 2011 and an increasing number of facilities of different types are participating in this data collection since then.Methods/DesignThis surveillance register collects information on every treatment episode started by patients for their substance use disorder. Information is collected on socio-demographic characteristics of the patient, treatment history and substance use patterns. Patients are identified uniquely using their national identification number in order identify multiple episodes followed by a same person. A large range of treatment facilities have the possibility to participate in this registration to allow a wide coverage of the population.DiscussionThe objective of the paper is to facilitate the use of data by authorities or researchers by correctly describing all aspects of the indicator. The case definition, the variables collected and the way data should be reported are of key importance to use and interpret the data correctly. An overview of the data registered in 2014 gives also an idea of the content of the database. The article also pictures the strengths and limitations of the register and foresees some future improvements.

Health care trajectories and medication consumption of substance users in treatment: linking TDI and IMA databases (Belgium)

Background As problem substance use has a relative low prevalence and is often socially stigmatised, it is rather difficult to study health care trajectories and medication consumption among substance users. In Belgium, the Treatment Demand Indicator register (TDI) is a major information source for drug epidemiology. However, it should be considered as an incidence register as only new drug-related treatment episodes are registered. Linkage with national compulsory health insurance data (IMA) will create a data source in which longitudinal and case-control studies can be performed.

Contents Vol. 11, 2011

99 43rd European Pancreatic Club (EPC) Meeting June 22–25, 2011, Magdeburg, Germany Guest Editor: Halangk, W. (Magdeburg) (available online only) 276 Erratum 277 IAP Society News 278 EPC Society News No. 3