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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.
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
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
A recent review revealed that mpUS is not widely studied
yet, but that early results are encouraging. mpUS might
serve as a cost-effective and safe diagnostic tool to select
patients for focal therapy and to plan treatment