Please activate JavaScript!
Please install Adobe Flash Player, click here for download

discovered 02_2012

discovered 02.12 FOCUS WWW.Hzdr.DE the next few cycles of cellular division. As this is the case for both tumor cells and healthy cells, the dose that can be applied to the tumor by external beam radiotherapy is limited by the potential risk of radiation-induced damage to healthy tissue. High-precision radiotherapy techniques like, for instance, proton therapy (protons are hydrogen nuclei), can help minimize this problem significantly. However, further improvements are absolutely necessary in order to be able to help more patients in the future. What is helpful here is the fact that radiation of different qualities and energies can be used. The HZDR researchers have access to a host of options for different radiation sources in their “toolbox.“ In addition to megavoltage X-rays from clinical linear accelerators or clinical proton beams, they use beta emitters such as yttrium-90, lutetium-177, or rhenium-188. These emit electrons from the atomic nucleus with a typical half-life. The half-life of lutetium-177, for example, is 160 hours, whereas that of yttrium-90 is approximately 65 hours. Radioactive half-life is an important factor for the preparation time in the laboratory and, later, in the clinical setting for the kinetics of dose-delivery in the tumor. On the other hand, the energy from the emitted electrons determines their range. Overall, the range of electrons compared to external beam radiation therapy is considerably less. Therefore, healthy tissues surrounding the cancer receive substantially lower doses than does the tumor itself. The toolbox has more to offer yet: depending on the size of the respective tumor or metastasis, using suitable radionuclides, tailor-made substances may be developed for internal radiation. In this way, for example, yttrium-90 with a maximum penetration depth of eleven millimeters would be used for treatment of relatively larger-size tumors, while electrons emitted by lutetium-177 with considerably lower energy (maximum range 1.8 mm) may be better suited to micrometastases. The combination of different radionuclides would also be a way to optimize efficacy. But the toolbox holds more potential still. Generally speaking, alpha emitters are also suitable for internal radiation. Compared with electrons, their large mass, made up of alpha-particles (i.e. helium nuclei), has a very low range on the order of several tens of micrometers in the tissues, meaning that they transfer their energy (of several megaelectron-volts) to the tissue along the way, resulting in severe damage to irradiated cancer cells, and thereby making this a highly effective potential anti- cancer weapon. Whichever radionuclide is used, the challenge is always one of accurately directing it to the cancer cells using mini-transporters without causing damage to other organs, such as bone marrow, the kidneys, or the liver. Therefore, the HZDR scientists have been hard at work on a variety of cancer-specific transport molecules – a very innovative and successful road to go down. Radiating transport with precision landing Using antibodies marked with radionuclides in an animal model, Dresden scientists were able to prove that internal radiation therapy combined with external beam radiation substantially increases tumor eradication rates. Antibodies are exceptionally large molecules that move only very slowly from the bloodstream into the tumor or metastasis. In this way, sometimes, it could take several days for such an antibody to accumulate in the cancer tissue. The long circulation time may lead to relatively high doses in healthy tissues. “Therefore, we are exploring the lock-and-key principle, according to which the radioactive component is only administered after the antibody has already attached itself to the cancer cells. In this way, the healthy tissues are much less exposed to unnecessary radiation. The radioactive substance (the ‘key’) is injected several days after the antibody. In the body, the key quickly and very specifically recognizes the matching antibody (the ‘lock’) and binds to it so that the radiation directly targets those tumor cells with the attached antibodies,“ explains Hans-Jürgen Pietzsch. The scientists are using two individual complementary DNA strands for their experiments. One strand is attached to the antibody, while the complementary strand is transporting the respective radionuclide. Once the two strands meet, they very quickly connect and become very stable – similar to the way a zipper works. Christian Förster, a scientist working in the Radiotherapeutics Division, has done research on this principle as part of his dissertation. “For the lock-and-key approach, we did not use naturally occurring DNA,“ Förster explains. “Instead, we modified the individual DNA strands in such a way that they were no longer recognizable by the COMBINATION: By combining diagnostic X-ray and computer tomography with state-of-the art radiation therapy, tumors can be irradiated more precisely. Other advantages include less damage to healthy tissues and fewer side effects. Image credit: Rainer Weisflog.