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ENCITE - Application of imaging methods to cell-based therapies: from basic research to clinical practice

The European Network for Cell Imaging and Tracking Expertise (ENCITE) presented some promising developments in cell therapy imaging techniques for cancer patients, to an enthusiastic audience at the European Congress of Radiology 2012, in Vienna. The progress made in the design of new probes and the rate of technological advance in monitoring disease and therapy has been rapid. In addition to the

The audience engaged in some interesting discussions on magnetic resonance imaging and multimodal preclinical imaging studies, which brought up a variety of questions, and both the audience and ENCITE experts shared their opinions. Philipp Boehm-Sturm, PhD student at the Max Planck Institute for Neurological Research in Cologne/DE, presented a new method of cell tracking using fluorine magnetic resonance imaging. Due to ENCITE’s keen interest in this new imaging modality, our scientists spent an intense eight-month period learning more about the potential capabilities and limits of this technique, the standards for making data more comparable and finally some answers to questions like ‘Can fMRI be combined with other modalities?’ and ‘How can it be used in the clinic?’ As a result, it is now possible, for the first time, to non-invasively assess the location, number and viability of cells to better monitor cell therapies, in cases of stroke, for example. “Today, Fluorine MRI is a really important modality in the preclinical phase” said Boehm-Sturm, who pointed out that within the next few years it may be used as a non-invasive control for implanted cell numbers in human research. The key issues discussed with the audience were related to the use of perfluorocarbon-based compounds and the expected results of assessing clearance processes of fluorinated cell labels. Wilfried Reichardt, medical physicist at the University Medical Center, Freiburg/DE, said that “it is possible to acquire multiple biomarkers for assessing therapy response, simultaneously and in vivo, which would be of great value for effective therapy monitoring.” Reichardt presented his research work, which focuses on the imaging of cell fate and therapy monitoring. One of the promising new treatment options in oncology is anti-angiogenic therapy for tumours. This therapy can be monitored using dynamic contrast-enhanced MRI or dynamic susceptibility contrast MRI and vessel size imaging (VSI) which detect changes in tumour microvasculature. He also showed that it is possible to show these changes specifically for those parts of the tumour that are most affected by the therapy. In the context of work carried out within the preclinical phase, prior to clinical imaging, a response to the challenges posed by new image analysis as compared to clinical imaging was presented by Boudewijn P.F. Lelieveldt, head of the Knowledge Guided Image Processing Section at the Leiden University Medical Center/NL. Lelieveldt’s areas of specialisation are in merging different types of biomedical images and the automated processing of image data, with specific software. The standard atlases for defining individual skeleton bones in mice were combined in order to find the similarities and differences between several images using side-by-side views, interactive MR super-resolution and automated bone volume measurement. The audience complimented Lelieveldt’s impressive images and asked him about his long-term plan to make this software available. “We don’t have commercial versions of this yet, but at some point we would like to make it available for life science groups who want to do research”, said Lelieveldt. Particular attention was paid to the significantly increasing need for training and education for researchers in the course of the physical system/service implementation of ENCITE’s techniques. Five participating organisations in Belgium, Israel, Italy, the Netherlands and Germany launched a multidisciplinary network in March, 2012 “offering access to specific training and an online repository of ENCITE probes and procedures”, said Silvio Aime, head of both the Molecular Imaging Center of the University of Torino/IT and the ENCITE Multi-Centre Cluster. Before bringing these new techniques to clinical practice and training, further research is necessary in order to figure out how imaging can optimise DC vaccination therapy in cancer patients. Carl Figdor, head of the Tumour Immunology Department at Nijmegen University Medical Center/NL, has been working for fifteen years on treating cancer patients and helping their immune system. Currently, “a platform with polylactic-co-glycolic acid ( PLGA) particles is being developed with the aim of looking not only at fluorine MR imaging in preclinical models, but also to see if this can be brought to the clinic.” said Figdor. In conclusion, the scientists pointed out that their latest developments are under evaluation for approval and will be considered for availability at a later stage: • Anti-angiogenesis has recently been approved for Glioblastoma and is now under clinical evaluation. • Regardless of the mouse’s position in a scanner, the currently used software programme is used to get corresponding views of skeleton bones next to each other, making it much easier to compare and track changes. To successfully compare different imaging modalities the future challenges to be mastered are keeping up with new imaging modalities which arise year-by-year and to further automate the processes for comparison. • The Food and Drug Administration (FDA) approved the first fluorine compound for clinical DC vaccines in a patient. • The process using new generation fluorinated PLGA particles is currently under evaluation and hopefully, clinical trials can be started by the end of 2012 using these particles within in vivo settings, for cancer patients. ENCITE’s scientists are confident that these technologies are speeding up developments in cell therapies and that their entry into wider routine clinical practice could offer potential cures for many types of cancer. Details on the latest news: www.encite.org ENCITE is co-funded by the European Commission under the 7th Framework Programme. For further information please contact: European Institute for Biomedical Imaging Research (EIBIR), Project Coordination Neutorgasse 9, 1010 Vienna (AT) Phone: +43-1-5334064-20 office@eibir.org www.eibir.org www.encite.org Scientific Coordinator: Prof. Gabriel P. Krestin, ERASMUS MC, ehaas@eibir.org

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Austria, Belgium, Bulgaria, Cyprus, Czechia, Germany, Denmark, Estonia, Greece, Spain, Finland, France, Hungary, Ireland, Italy, Lithuania, Luxembourg, Latvia, Malta, Netherlands, Poland, Portugal, Romania, Sweden, Slovenia, Slovakia, United Kingdom

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