Investigations on the Usefulness of CEACAMs as Potential Imaging Targets for Molecular Imaging Purposes

Members of the carcinoembryonic antigen cell adhesion molecules (CEACAMs) family are the prototype of tumour markers. Classically they are used as serum markers, however, CEACAMs could serve as targets for molecular imaging as well. In order to test the anti CEACAM monoclonal antibody T84.1 for imaging purposes, CEACAM expression was analysed using this antibody. Twelve human cancer cell lines from different entities were screened for their CEACAM expression using qPCR, Western Blot and FACS analysis. In addition, CEACAM expression was analyzed in primary tumour xenografts of these cells. Nine of 12 tumour cell lines expressed CEACAM mRNA and protein when grown in vitro. Pancreatic and colon cancer cell lines showed the highest expression levels with good correlation of mRNA and protein level. However, when grown in vivo, the CEACAM expression was generally downregulated except for the melanoma cell lines. As the CEACAM expression showed pronounced expression in FemX-1 primary tumours, this model system was used for further experiments. As the accessibility of the antibody after i.v. application is critical for its use in molecular imaging, the binding of the T84.1 monoclonal antibody was assessed after i.v. injection into SCID mice harbouring a FemX-1 primary tumour. When applied i.v., the CEACAM specific T84.1 antibody bound to tumour cells in the vicinity of blood vessels. This binding pattern was particularly pronounced in the periphery of the tumour xenograft, however, some antibody binding was also observed in the central areas of the tumour around blood vessels. Still, a general penetration of the tumour by i.v. application of the anti CEACAM antibody could not be achieved despite homogenous CEACAM expression of all melanoma cells when analysed in tissue sections. This lack of penetration is probably due to the increased interstitial fluid pressure in tumours caused by the absence of functional lymphatic vessels.Germany. Bundesministerium für Bildung und Forschung (TOMCAT, grant number 01EZ0824

Restrictions of VC and DLCO in relation to asbestos-related computed tomographic findings quantified by ICOERD-based parameters

BACKGROUND: Even almost 30 years after the ban on the use of asbestos in Germany, the effects of asbestos are still highly relevant in everyday clinical practice in occupational medicine. The aim of this study was to further investigate the significance of essential parameters of both pulmonary function diagnostics and imaging techniques (low-dose HR-TCT) for the prevention and early detection of asbestos-related morphological and functional lung changes. METHODS: Data from spirometry, body plethysmography and diffusion capacity, as well as CT images of the thorax, were retrospectively studied from 72 patients examined between 2017 and 2019 at the Institute for Occupational and Maritime Medicine (ZfAM), Hamburg, Germany. The subjects were divided into four subgroups according to the presence of comorbidities (concomitant cardiac diseases, obstructive ventilatory disorder, pulmonary function pattern consistent with emphysema, and no other pulmonary or cardiac diseases). These subgroups were analysed in addition to the overall collective. The CT images were evaluated according to the International Classification of Occupational and Environmental Respiratory Diseases (ICOERD) with radiological expertise. In addition, some asbestos-related parameters were newly quantified, and corresponding scores were defined based on ICOERD. Statistical analysis included the use of correlations and fourfold tables with calculation of Spearman's rho (ρ), Cohen’s κ, and accuracy. RESULTS: Vital capacity (VC) is slightly reduced in the total collective compared to the normal population (mean 92% of predicted value), while diffusion capacity for CO (DLCO) shows predominantly pathological values, mean 70% of the respective predicted value. The CO transfer coefficient (DLCO/VA), which refers to alveolar volume (VA), also shows slightly decreased values (mean 87% pred.). Seventy-nine percent of patients (n = 57) had signs of pulmonary fibrosis on CT scans, and pleural plaques appeared in 58 of 72 patients (81%). Of the newly quantified additional parameters, particularly frequently described findings are subpleural curvilinear lines (SC, n = 39) and parenchymal bands (PB, n = 29). VC correlates well with the expression of pleural plaques (ρ = − 0.273, P < 0.05), and DLCO measures show a better correlation with fibrosis score (ρ = − 0.315, P < 0.01). A third, newly developed score, which includes the extent of pleural plaques and additional subpleural parameters instead of fibrosis parameters, shows significant correlations for both VC and DLCO (ρ = − 0.283, − 0.274, resp.; both P < 0.05). DISCUSSION: The importance of spirometry (VC) and diffusion capacity measurement (DLCO) as essential diagnostic procedures for the early detection of asbestos-related changes ‒ also including patients with relevant concomitant cardiac or pulmonary diseases ‒ was confirmed. Significant and better correlations between lung function changes (VC and DLCO) and abnormal CT findings are seen when parenchymal bands (PB), subpleural curvilinear lines (SC), and rounded atelectasis (RA) are quantitatively included into the evaluation, in addition to assessing the extent of pleural plaques alone. Therefore, when assessing CT images according to ICOERD, these parameters should also be quantified

Infectious complications of radiologically placed upper arm ports: A single center analysis

Objectives Infections are common complications in venous access ports. The presented analysis aimed to investigate the incidence, microbiological spectrum, and acquired resistances of pathogens in upper arm port associated infections to provide a decision aid in the choice of therapy. Materials and methods In total, 2667 implantations and 608 explantations were performed at a high-volume tertiary medical center between 2015 and 2019. In cases with infectious complications (n = 131, 4.9%), procedural conditions and results of microbiological testing were reviewed retrospectively. Results Of 131 port associated infections (median dwell time 103 days, interquartile range 41–260), 49 (37.4%) were port pocket infections (PPI) and 82 (62.6%) were catheter infections (CI). Infectious complications occurred more often after implantation in inpatients compared to outpatients (P Conclusions Staphylococci comprised the largest group of pathogens in upper arm port associated infections. However, gram-negative strains and Candida species should also be considered as a cause of infection in CI. Due to the frequent detection of potential biofilm-forming pathogens, port explantation is an important therapeutic measure, especially in severely ill patients. Acquired resistances must be anticipated when choosing an empiric antibiotic treatment

Infectious complications of radiologically placed upper arm ports: A single center analysis.

ObjectivesInfections are common complications in venous access ports. The presented analysis aimed to investigate the incidence, microbiological spectrum, and acquired resistances of pathogens in upper arm port associated infections to provide a decision aid in the choice of therapy.Materials and methodsIn total, 2667 implantations and 608 explantations were performed at a high-volume tertiary medical center between 2015 and 2019. In cases with infectious complications (n = 131, 4.9%), procedural conditions and results of microbiological testing were reviewed retrospectively.ResultsOf 131 port associated infections (median dwell time 103 days, interquartile range 41-260), 49 (37.4%) were port pocket infections (PPI) and 82 (62.6%) were catheter infections (CI). Infectious complications occurred more often after implantation in inpatients compared to outpatients (P ConclusionsStaphylococci comprised the largest group of pathogens in upper arm port associated infections. However, gram-negative strains and Candida species should also be considered as a cause of infection in CI. Due to the frequent detection of potential biofilm-forming pathogens, port explantation is an important therapeutic measure, especially in severely ill patients. Acquired resistances must be anticipated when choosing an empiric antibiotic treatment

Antibody directed against human YKL-40 increases tumor volume in a human melanoma xenograft model in scid mice

Induced overexpression of the secretory protein YKL-40 promotes tumor growth in xenograft experiments. We investigated if targeting YKL-40 with a monoclonal antibody could inhibit tumor growth. YKL-40 expressing human melanoma cells (LOX) were injected subcutenously in Balb/c scid mice. Animals were treated with intraperitoneal injections of anti-YKL-40, isoptype control or PBS. Non-YKL-40 expressing human pancreatic carcinoma cell line PaCa 5061 served as additional control. MR imaging was used for evaluation of tumor growth. Two days after the first injections of anti-YKL-40, tumor volume had increased significantly compared with controls, whereas no effects were observed for control tumors from PaCa 5061 cells lacking YKL-40 expression. After 18 days, mean tumor size of the mice receiving repeated anti-YKL-40 injections was 1.82 g, >4 times higher than mean tumor size of the controls (0.42 g). The effect of anti-YKL-40 on the increase of tumor volume started within hours after injection and was dose dependent. Intratumoral hemorrhage was observed in the treated animals. The strong effect on tumor size indicates important roles for YKL-40 in melanoma growth and argues for a careful evaluation of antibody therapy directed against YKL-40

Case characteristics of port pocket infections (PPI) and catheter infections (CI).

Case characteristics of port pocket infections (PPI) and catheter infections (CI).</p

Isolates with distinct susceptibility tests and frequency of strains with acquired resistances in port pocket infections and in catheter infections.

Isolates with distinct susceptibility tests and frequency of strains with acquired resistances in port pocket infections and in catheter infections.</p

Quantitative Magnetic Resonance Imaging of Enzyme Activity on the Cell Surface: In Vitro and In Vivo Monitoring of ADP-Ribosyltransferase 2 on T Cells

The objective of this study was to quantify enzymatic activity on the surface of T cells by magnetic resonance imaging (MRI) using R2 and R2* relaxometry. Lymphoma cells expressing adenosine diphosphate (ADP)-ribosyltransferase 2 (ART2) were incubated with increasing doses of its substrate etheno–nicotinamide adenine dinucleotide (NAD), resulting in increasing amounts of surface protein ADP-ribosylation. Etheno-ADP-ribosylated proteins were detected with monoclonal antibody 1G4 and superparamagnetic iron oxide conjugated secondary antibodies (Ab-SPIO). Labeling efficiency was determined with R2 and R2* relaxometry on a clinical 3.0 T scanner. Parallel aliquots of cells were analyzed by flow cytometry. Cell-bound SPIO conjugates were detected by immunofluorescence and electron microscopy and quantified by atomic absorption spectroscopy. To mimic an inflammatory site in vivo, Ab-SPIO-labeled cells were injected subcutaneously in mice and analyzed by MRI. Immunofluorescence and electron microscopy confirmed cell-surface localization of Ab-SPIO. MRI of Ab-SPIO-labeled cells showed a corresponding signal reduction. Increases in R2 and R2* determined by magnetic resonance relaxometry correlated linearly with the expression level of ART2 and the concentration of the ART2 substrate etheno-NAD. R2 and R2* increases correlated linearly with the results from flow cytometry and atomic absorption spectroscopy analyses. Quantitative R2 and R2* mapping enable noninvasive determination of enzymatic activity on T cells and holds promise for characterization of inflammatory sites in vivo by MRI

Bard Titanium SlimPort^TM.

Fluoroscopic image of a Bard Titanium SlimPortTM with a 6F single lumen polyurethane catheter in typical location at the distal upper arm.</p

Subgroup analysis of catheter infections (CI).

Group 2.1: CI with matching isolates from blood cultures and the port catheter tip (a). Group 2.2: CI with positive blood culture results and negative culture of the port catheter tip (b). Coagulase-negative staphylococci–CoNS, species–spp.</p