Back
In vivo demonstration of an active tumor pretargeting approach with peptide nucleic acid bioconjugates as complementary system.
Journal article

In vivo demonstration of an active tumor pretargeting approach with peptide nucleic acid bioconjugates as complementary system.

  • Leonidova A Department of Chemistry , University of Zurich , Winterthurerstrasse 190 , CH-8057 Zurich , Switzerland . Email: gilles.gasser@chem.uzh.ch ; http://www.gassergroup.com ; Tel: +41 44 635 46 30.
  • Foerster C Helmholtz-Zentrum Dresden - Rossendorf , Institute of Radiopharmaceutical Cancer Research , Bautzner Landstraße 400 , D-01328 Dresden , Germany . Email: h.stephan@hzdr.de ; http://www.hzdr.de/NanoscalicSystems ; Tel: +49 351 260-3091.
  • Zarschler K Helmholtz-Zentrum Dresden - Rossendorf , Institute of Radiopharmaceutical Cancer Research , Bautzner Landstraße 400 , D-01328 Dresden , Germany . Email: h.stephan@hzdr.de ; http://www.hzdr.de/NanoscalicSystems ; Tel: +49 351 260-3091.
  • Schubert M Helmholtz-Zentrum Dresden - Rossendorf , Institute of Radiopharmaceutical Cancer Research , Bautzner Landstraße 400 , D-01328 Dresden , Germany . Email: h.stephan@hzdr.de ; http://www.hzdr.de/NanoscalicSystems ; Tel: +49 351 260-3091.
  • Pietzsch HJ Helmholtz-Zentrum Dresden - Rossendorf , Institute of Radiopharmaceutical Cancer Research , Bautzner Landstraße 400 , D-01328 Dresden , Germany . Email: h.stephan@hzdr.de ; http://www.hzdr.de/NanoscalicSystems ; Tel: +49 351 260-3091.
  • Steinbach J Helmholtz-Zentrum Dresden - Rossendorf , Institute of Radiopharmaceutical Cancer Research , Bautzner Landstraße 400 , D-01328 Dresden , Germany . Email: h.stephan@hzdr.de ; http://www.hzdr.de/NanoscalicSystems ; Tel: +49 351 260-3091.
  • Bergmann R Helmholtz-Zentrum Dresden - Rossendorf , Institute of Radiopharmaceutical Cancer Research , Bautzner Landstraße 400 , D-01328 Dresden , Germany . Email: h.stephan@hzdr.de ; http://www.hzdr.de/NanoscalicSystems ; Tel: +49 351 260-3091.
  • Metzler-Nolte N Lehrstuhl für Anorganische Chemie I - Bioanorganische Chemie , Fakultät für Chemie und Biochemie , Ruhr-Universität Bochum , Universitätsstrasse 150 , D-44801 Bochum , Germany.
  • Stephan H Helmholtz-Zentrum Dresden - Rossendorf , Institute of Radiopharmaceutical Cancer Research , Bautzner Landstraße 400 , D-01328 Dresden , Germany . Email: h.stephan@hzdr.de ; http://www.hzdr.de/NanoscalicSystems ; Tel: +49 351 260-3091.
  • Gasser G Department of Chemistry , University of Zurich , Winterthurerstrasse 190 , CH-8057 Zurich , Switzerland . Email: gilles.gasser@chem.uzh.ch ; http://www.gassergroup.com ; Tel: +41 44 635 46 30.
Show more…
  • 2018-06-05
Published in:
  • Chemical science. - 2015
English A novel, promising strategy for cancer diagnosis and therapy is the use of a pretargeting approach. For this purpose, the non-natural DNA/RNA analogues Peptide Nucleic Acids (PNAs) are ideal candidates as in vivo recognition units due to their high metabolic stability and lack of unspecific accumulation. In the pretargeting approach, an unlabeled, highly specific antibody-PNA conjugate has sufficient time to target a tumor before administration of a small fast-clearing radiolabeled complementary PNA that hybridizes with the antibody-PNA conjugate at the tumor site. Herein, we report the first successful application of this multistep process using a PNA-modified epidermal growth factor receptor (EGFR) specific antibody (cetuximab) and a complementary 99mTc-labeled PNA. In vivo studies on tumor bearing mice demonstrated a rapid and efficient in vivo hybridization of the radiolabeled PNA with the antibody-PNA conjugate. Decisively, a high specific tumor accumulation was observed with a tumor-to-muscle ratio of >8, resulting in a clear visualization of the tumor by single photon emission computed tomography (SPECT).
Language
  • English
Open access status
gold
Identifiers
Persistent URL
https://fredi.hepvs.ch/global/documents/4996
Statistics
Document views: 11 File downloads: