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discovered_02_2013

PORTRAIT// The HZDR Research Magazine WWW.Hzdr.DE 34 35 The radiation oncologist’s special focus has been on merging biological research findings with technological advances made in radiation therapy. As such, one of the things Baumann is looking at are candidate biomarkers that are good predictors of tumor radiosensitivity. In one clinical trial, he and his team were able to show that tumors of the head and neck that are deprived of oxygen are extremely resistant to radiation therapy. "Chances of healing largely depend upon individual biological factors," explains Baumann. "These have to be studied to allow us to customize the radiation dose for each individual tumor." Precise measurements of the radiation dose To improve the precision of radiotherapy – such is also Christian Richter’s goal. Richter, who is head of a research group at OncoRay, has devised a reliable technology for obtaining precise real-time measurements of the radiation dose of laser-accelerated, ultrashort pulsed particle beams. This is yet another step in the direction of progress along the way to future cancer treatment options using laser- accelerated proton beams. Because similarly to the big conventional accelerator facilities, laser light is capable of powering protons in such an intense way that they may be used in the fight against tumors in future. Until now, however, the biological effect of laser-accelerated particle beams has largely been unknown. Thanks to Richter’s study, this issue could at long last be addressed by applying his precise dose-measurement methodology in radiobiological experiments. This has allowed the researchers to obtain reliable initial experimental data on these rays’ biological efficacy – a necessary prerequisite for using laser-accelerated protons and electrons in cancer therapy. Thanks to this achievement, Christian Richter was able to come in second for the Behnken Berger Award, which earned him 10,000 Euro. This recognition is given by the endowment of the same name to junior scientists who are working on an application of radiation in medicine or on radiation protection. Fight from inside and out Whereas radiation therapy, which is already used to treat some 50 percent of all cancer patients, targets diseased cells and destroys them using radiation that is introduced into the body from outside, other research conducted at the HZDR actually starts from inside the body. What is known as endoradionuclide therapy will ultimately target tumors and damage them by delivering radioactive substances directly to the cancer cell. The path is laid out for them by specialized antibodies, for instance, which travel to the site of the tumor as transport molecules via the bloodstream, and dock to the tumor. These antibodies can either be directly radioactively labeled or, alternatively, they may initially label the tumor cell, which, in a second step, is followed by injection of the radiation source. Think of it as a key fitting in a lock – because the scientists are using two artificial complementary single strands of DNA, one of which attaches to the antibody, the other to the radioactive substance. When they contact each other, the two substances rapidly form a highly stable compound. For this, modified DNA is used, which the organism no longer recognizes as DNA but which maintains its binding property by virtue of this "lock-and-key" principle. Christian Förster has gone ahead and modified one of the single DNA strands in such a way as to be able to attach the therapeutic radionuclide to it. Once inside the organism, this radioactively labeled single strand exhibits near perfect properties: For one, it circulates long enough for it to locate the complementary DNA strand with its attached antibody; for another, only little accumulates in those organs that are especially radiosensitive. Also, the single DNA strand is not degraded in the bloodstream. In the end, there is but one choice for binding site left inside the organism, that is to those antibodies carrying the complementary DNA strand and which mostly accumulated in the tumor tissue. The radioactive substance thus unfolds its destructive potential for the most part right at the diseased cells while the rest of the organism is safe from radiation exposure. In recognition of this research, the German Chemical Society’s Subdivision of Nuclear Chemistry presented Förster with its Ph.D. Award. Yet it isn’t only cancer treatment but also precise diagnostics and tumor characterization that are integral to the successful fight against the disease, all of which are important research emphases at the HZDR. As such, Reik Löser’s junior research group recently developed a new peptide-based radiotracer. The tracer, which is labeled with the radionuclide fluoride-18, is used to visualize activity of the enzyme lysyl oxidase, which plays an important role in cancer. "We used PET imaging to prove the uptake of the tracer by the neoplastic tissues of three different types of breast cancer tumors," explains Manuela Kuchar, who is part of the junior research group. For her presentation of these research findings, the Ph.D. student recently received the Best Presentation Award at the Radiochemistry/Radiopharmacy Work Group’s Annual Conference. Contact _Institute of Radiooncology at HZDR / National Center for Radiation Research in Oncology – OncoRay Prof. Michael Baumann michael.baumann@uniklinikum-dresden.de _ National Center for Radiation Research in Oncology – OncoRay Dr. Christian Richter christian.richter@oncoray.de _Cross Cancer Institute in Edmonton, Alberta (since 04.2013) Dr. Christian Förster cfoerste@ualberta.ca _Institute of Radiopharmaceutical Cancer Research at HZDR Manuela Kuchar m.kuchar@hzdr.de

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