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discovered 02_2012

discovered 02.12 FOCUS WWW.Hzdr.DE Surgery, external beam radiotherapy, and chemotherapy are the three pillars of current-day cancer treatment. Using these different types of treatment, approximately 50 percent of cancer patients can successfully be cured. The odds of being cured are compromised significantly, however, if cancer cells are allowed to spread from the primary tumor to form metastases in other, more distant parts of the body. Today, the primary modality for attacking metastatic cancer is systemic chemotherapy. However, only very small metastases containing only a very small number of cancer cells – oncologists refer to these tumors as micrometastases – can be permanently eradicated by application of currently available chemotherapeutic drugs. Therefore, new and more efficient therapeutic approaches are urgently warranted. Cancer researchers at the Helmholtz-Zentrum Dresden- Rossendorf are committed to the development of novel radioactive substances, which might be used to improve detection and combat of primary tumors and their associated metastases. As such, research conducted at the HZDR‘s Institute of Radiopharmacy is focused on the development of radiopharmaceutial tracers and drugs capable of specifically targeting and destroying tumor cells as well as on evaluation and improvement of novel combined imaging methods like the positron-emission tomography and magnetic-resonance imaging (PET/MRI) hybrid. The successful clinical application of this research both now and in the future depends upon the close collaborative partnership that exists between the HZDR and the University Hospital Dresden at the OncoRay Center. Micrometastases Microscopically small metastases, or small clusters of only a few cancer cells, frequently evade detection and thus, by definition, diagnosis – a condition known as a subclinical disease. Even the most modern-day imaging techniques, including those capable of simultaneously producing PET- and MRI-scans of the entire body at high resolutions – which are available at the HZDR – are only able to detect metastases with diameters of give or take a few millimeters. However, if metastases go undetected, doctors may not prescribe the necessary systemic therapies as they may be under the (false!) impression that the tumor has not yet spread to other parts of the body. Or, conversely, based on past experience, doctors might prescribe systemic treatment for every single patient who is statistically at a risk for metastases, which would lead to over-treatment of a substantial number of patients in whom the primary tumor did not metastasize. Therefore, it is very important that new radiopharmaceutical substances and imaging technologies capable of tracing smaller metastases are being developed to help doctors make more personalized decisions based on a patient‘s individual risk profile. Equally as important is the continued development of new radiopharmaceutical anti-cancer drug treatments capable of targeting microscopic – and macroscopic – metastases and tumors. At this time, radioiodine therapy of the thyroid has proved an extremely successful example for imaging and internal radiotherapy using radionuclide iodine-131. For the past 70 years, radioiodine therapy has successfully been used in cancer diagnosis and treatment and as a diagnostic and treatment tool in thyroid disease. Since only those cells of the thyroid that are normally in charge of making thyroid hormone store iodine, radioactive isotopes of iodine specifically target only the hormone-producing cells – regardless of whether the thyroid has become enlarged, or cancerous, or if cancer cells have metastasized. This clinically approved radionuclide therapy (or endoradionuclide therapy) is the archetype for new internal radiation therapeutic approaches in oncology. A mere ten years ago, research aimed at broadening the spectrum of radiopharmaceutical drugs for use in cancer therapy was only done by a handful of groups – and, unfortunately, all too often the new drugs turned out to be nonspecific and ineffective, precluding their introduction into the clinical setting. Fairly recently, substantial progress has been made by combining external beam irradiation, which is well established in clinical cancer radiotherapy, with novel and the more highly specific internal radiation modalities. Exploiting the tumor’s metabolic profile “Our plan is to use our new radioactive substances to enhance the effects of external beam radiotherapy on the primary tumor and at the same time destroy metastatic cells, which may be hiding out somewhere else in the body. This would allow doctors to increase the overall radiation dose to the primary tumor without inflicting more damage on the surrounding healthy tissues. At the same time, any potential metastases would also be targeted for destruction. Doctors are hopeful that this approach can widen the therapeutic window and that more patients can ultimately be cured,“ explains Hans-Jürgen Pietzsch, head of the HZDR‘s Radiotherapeutics Division. To reach this ultimate goal, he and his team are currently pursuing two different research strategies: one based on antibodies for transporting radioactive nuclear components that stay in the circulation for a longer period of time; the other based on using smaller molecules like peptides or small proteins capable of quick dispersal within the body. Regardless of which one of these two very different approaches ultimately proves more successful from a radio- pharmaceutical vantage point, what is important is that the unique properties of cancer cells are exploited to facilitate the transport of molecules for delivering the radionuclide to the site of the primary tumor or the metastasis. Given their uncharacteristically high degree of metabolic activity, tumor cells consume a lot more energy than do healthy tissues. This difference in a tumor‘s metabolic profile has been exploited successfully for many years by the intravenously injected, radioactively labeled sugar 18-fluorodeoxyglucose, which is used in detecting cancer as tumor cells take up this sugar at higher rates than do normal cells. Other options for utilizing the increased metabolic activity of cancer cells for medical imaging purposes include radiotracers based on amino acids or nucleic acid components.