Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Molecular Spies to Fight Cancer - Procedure for improving tumor diagnosis successfully tested

03.08.2015

Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR), in cooperation with colleagues at the University of Zurich and the Ruhr-Universität Bochum, have for the first time successfully tested a new tumor diagnosis method under near-real conditions. The new method first sends out an antibody as a "spy" to detect the diseased cells and then binds to them. This antibody in turn attracts a subsequently administered radioactively labeled probe. The scientists could then clearly visualize the tumor by utilizing a tomographic method. This procedure could improve cancer treatment in the future by using internal radiation.

The human immune system forms antibodies that protect the body from pathogens. Antibodies can also, however, be produced in a laboratory to precisely bind to tumor cells. They are used in cancer research to detect and fight malignant tumors. For example, antibodies can serve as transport vehicles for radionuclides, with which the affected regions can be visualized or can even be damaged. Until recently, a stumbling block has been their large molecular mass.


PNA-antibodies detect initially the diseased cells (red) and accumulate at the tumor site. Afterwards the radioactively labeled probes (blue) selectively bind to them by specific base pairing.

HZDR/Pfefferkorn

“This causes them to circulate in the body for too long before they reach the diseased cells,” explains Dr Holger Stephan from the Institute of Radiopharmaceutical Cancer Research at HZDR. "This is a disadvantage because organs that are not affected by the disease are exposed to radiation. It also makes the exact localization of the tumor in the body more difficult because the resulting images are less sharp.”

Together with colleagues at the University of Zurich and the Ruhr-Universität Bochum, the researchers from Dresden therefore chose an alternative strategy. “By using what is known as ‘pre-targeting’, the antibodies’ task is divided into two steps,” Dr Kristof Zarschler, a member of Stephan's team, explains. “In a figurative sense, we first send spies out in advance, over a longer period of time, to scout out the enemy – the tumor cells.

The ‘spies’ then share their position with their troops, which we subsequently send out so that they will directly reach their target with the radioactive material.” The researchers fall back on the cetuximab antibody as the scout, which binds selectively to the epidermal growth factor receptor (EGFR). In various types of tumors, there is an increase in this molecule’s formation or it might be found in a mutated form, which then leads the cells to grow and multiply uncontrolled.

Clear Visualization

The Dresden researchers combined the antibody with a peptide nucleic acid (PNA) derivative which Prof Gilles Gasser and Prof Nils Metzler-Nolte developed together with their respective working groups in Switzerland and Germany. “It is a very stable synthetic variant of DNA," says Holger Stephan. “Similar to a single strand of DNA, it consists of a certain sequence of the four organic bases. Complementary PNA with matching sequence binds to it in a highly precise and stable manner.”

During their experiments, the scientists first injected the PNA-EGFR antibody into tumor-bearing mice and gave this “spy” time to accumulate at the tumor site. They then administered the PNA counterpart, labeled with the radioactive substance technetium-99m. “Images we took using single photon emission computed tomography show that both the antibody and its counterpart located each other quickly,” says Zarschler, pleased with the results.

The tumor could thus be clearly visualized within a short period of time. “Furthermore, the radioactively labeled probes had already disappeared from the bloodstream after sixty minutes,” explains Holger Stephan. “This minimizes radioactive exposure risk of healthy body tissue. By pre-targeting, we can overcome limitations of conventional, radioactively marked antibodies.” According to the researchers, it will, however, take some time before the combination of PNA antibodies and their matching PNA counterparts can be used in diagnosing tumors in humans.

“Our results however show that the PNAs we tested are suitable candidates for further preclinical studies,” Stephan sums up. They could provide new possibilities not only for visualizing diseased cells but also for fighting them. “If the method is proven to work, it could also be used to transport therapeutically effective radioactive substances to the tumor in order to irradiate it from within and ultimately damage it.”

Publication:
A. Leonidova, C. Foerster, K. Zarschler, M. Schubert, H. Pietzsch, J. Steinbach, R. Bergmann, N. Metzler-Nolte, H. Stephan, G. Gasser, „In vivo demonstration of an active tumor pretargeting approach with peptide nucleic acid bioconjugates as complementary system”, in: Chemical Science (2015), DOI: 10.1039/c5sc00951k

Further Information:
Dr. Holger Stephan
Institute of Radiopharmaceutical Cancer Research at HZDR
Phone +49 351 260-3091 | E-Mail: h.stephan@hzdr.de

Prof. Gilles Gasser
Department of Chemistry at the University of Zurich
Phone +41 44 63 54630 | E-Mail: gilles.gasser@chem.uzh.ch

Media Contact:
Simon Schmitt | Science editor
Phone +49 351 260-3400 | E-Mail: s.schmitt@hzdr.de
Helmholtz-Zentrum Dresden-Rossendorf
Bautzner Landstr. 400 | 01328 Dresden, Germany | www.hzdr.de

Weitere Informationen:

http://www.hzdr.de/db/Cms?pNid=99&pOid=45202

Simon Schmitt | Helmholtz-Zentrum Dresden-Rossendorf

Further reports about: CANCER DNA Helmholtz-Zentrum Molecular acid diagnosis sequence tumor cells

More articles from Life Sciences:

nachricht Designed proteins to treat muscular dystrophy
29.06.2017 | Universität Basel

nachricht Funding of Collaborative Research Center developing nanomaterials for cancer immunotherapy extended
28.06.2017 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

High conductive foils enabling large area lighting

29.06.2017 | Power and Electrical Engineering

Designed proteins to treat muscular dystrophy

29.06.2017 | Life Sciences

Climate Fluctuations & Non-equilibrium Statistical Mechanics: An Interdisciplinary Dialog

29.06.2017 | Seminars Workshops

VideoLinks
B2B-VideoLinks
More VideoLinks >>>