ESTRO 36 Abstract Book

S11 ESTRO 36 _______________________________________________________________________________________________

Material and Methods Primary Human Umbilical Vein Endothelial Cells (HUVECs) were irradiated at 20 Gy ( 137 Cs source) and studied from 12 hours to 21 days. Glycosylation was studied by fluorescence microscopy and flow cytometry using a set of fluorescent lectins to specifically quantify different types of sugar. The overall N-glycan pattern was studied by MALDI-TOF mass spectrometry. Glycosaminoglycans were studied by the uronic acid dosage. Interactions of endothelial cells with fluorescent THP-1 monocytes were analyzed under flow conditions by fluorescence videomicroscopy. Radiation enteropathy of C57BL/6 mice was induced by exposure of an intestinal segment to 19 Gy of radiation (LINAC, 4 MV) and studied at day 3, 7 and 42. The mRNA levels of 84 genes encoding proteins involved in glycosylation were measured in HUVECs and small intestine by real-time quantitative PCR using human or mouse glycosylation PCR array. Results We show here that ionizing radiation induces an overexpression of high mannose-type N-glycans at the membrane surface of primary endothelial cells, while complex-type N-glycans decrease. We also show a decrease of the quantity of glycosaminoglycans upon radiation exposure, which may reflect a thinning of the glycocalyx. Using fluorescence videomicroscopy, we show that these changes contribute to increase monocyte adhesion on irradiated HUVECs under flow conditions. By a transcriptomics approach, we confirmed that genes involved in N-glycosylation are modulated by ionizing radiation. We also show that O-glycosylation is probably modified by radiation, which we validated by cell labeling experiments using fluorescent lectins. Finally, we studied the expression of a panel of genes involved in glycosylation in a radiation enteropathy mouse model, showing that a global modification of glycosylation gene expression occurs in the irradiated small intestine. Conclusion Our results demonstrate the existence of radiation- induced changes of endothelial glycosylation in vitro , with functional consequences on the adhesion of monocytes. They also suggest that irradiation modifies the glycosylation pattern of the small intestine tissue. In the same way as in chronic disease such as atherosclerosis, the endothelium glycome therefore appears to be a therapeutic target for modulating the pathological inflammatory response observed after irradiation.

assurance while endoscopy is principally used to guide applicator insertion for lung and esophagus brachytherapy. This presentation will briefly discuss new techniques in endoscopy; introduce several evolving optical imaging modalities that are proving valuable in intraluminal disease detection. For instance, white light endoscopy has long played a critical role in diagnostics and disease staging of cancer for many intraluminal sites. With the advent of laparoscopic surgery, endoscopy is also critical for minimally invasive surgery. Endoscopic microscopy is also offering new methods of visualizing disease at fields of view that are possibly relevant for brachytherapy. Fluorescence imaging, both with and without contrast agents, has been explored for disease detection in many disease sites. Advances in targeted contrast agents and imaging technology have created new opportunities in image guided surgery, in which fluorescence is used to detect microscopic levels of disease at tumour and surgical margins. and optical coherence tomography. Optical coherence tomography (OCT) provides almost pathology-like imaging for intraluminal sites that may be useful in assigning patient specific prescription depth information. The presentation will also outline applications of EM navigation in other fields, such as bronchoscopic and endoscopic navigation. We discuss possible roles for endoscopic navigation in brachytherapy, such as applicator placement for intraluminal sites and improved contouring of superficial disease. Navigation technologies have become commonplace in surgery and interventional radiology while endoscopic tracking integrated with volumetric imaging presents new “augmented” methods of visualizing clinical information. As applicators become more sophisticated improved methods of guiding their insertion are needed and navigation technologies are sure to play a role, not only in catheter reconstruction but also for placement guidance. Given the small role that each of these technologies currently has in brachytherapy this presentation will be, by necessity, somewhat speculative but it is hoped that this encourages further consideration on how to implement these technologies in brachytherapy. SP-0034 Using multiparametric US to redefine target volumes in brachytherapy H. Wijkstra 1 1 Eindhoven University of Technology / AMC University Hospital Amsterdam, Signal Processing Systems / Urology, Eindhoven / Amsterdam, The Netherlands Introduction Prostate cancer most often is characterised by multiple areas of malignant lesions that differ in size and morphologic appearance. The lesions can be divided in insignificant and dominant lesions (DLs). Using radiotherapy, identification of DLs would enable treatment of the whole prostate with a moderate dose and giving a boost on the DLs, which most probably will improve treatment outcome. To be able to localise DLs an accurate imaging technique is needed. Multiparametric MRI (mpMRI) has been developed as an imaging technique to detect and localise prostate cancer. In mpMRI a combination of T2 imaging, diffusion-weighted imaging (DWI) and dynamic contrast enhanced MRI (DCE- MRI) is used. Expert centers published promising results, however, recent studies demonstrate that mpMRI is still missing up to ~20% of significant prostate cancer. mpMRI is currently the main modality for the (pre-)planning of therapy, however, real-time ultrasound is used during most therapeutic procedures (e.g. brachytherapy). As compared to (mp)MRI, ultrasound is cost-effective, practical and widely available. A relative new development is multi parametric ultrasound (mpUS). Multi-parametric ultrasound

Symposium: Expanding brachytherapy indications

SP-0032 The technique for CT/MR guided hepatic implantations N.Tselis 1 1 Department of Radiation Oncology,Klinikum Offenbach GmbH, Germany

Abstract not received

SP-0033 Optical and tracking technologies for navigation in brachytherapy R. Weersink 1 1 Princess Margaret Cancer Centre University Health Network, Physical Chemistry, Toronto, Canada This presentation discusses two medical fields not normally associated with brachytherapy: optical imaging and image-guided navigation technologies. Both of these fields, especially in combination with each other, offer some new approaches to treatment planning and delivery in brachytherapy. To date, endoscopy and surgical navigation tools have had only limited roles in brachytherapy; electromagnetic (EM) tracking is under evaluation for catheter segmentation and quality

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