Publikationsrepositorium - Helmholtz-Zentrum Dresden-Rossendorf
1 PublikationRadiopharmaceutical Evaluation of Peptide Nucleic Acid Bioconjugates as Complementary System for Tumor Targeting
Stephan, H.
Abstract
The search for novel strategies for the diagnosis and therapy of cancer is currently a field of active research. A promising option is the use of a pretargeting approach with the non-natural DNA/RNA analogues Peptide Nucleic Acids (PNAs) as in vivo recognition units. Such a concept overcomes major drawbacks present when conventional monoclonal antibodies (mAbs) are employed as tumor-targeting agents by decoupling the delivery of a tumor-specific mAb from the delivery of the diagnostic or therapeutic radionuclide. In this multistep process an unlabeled, highly specific antibody-PNA conjugate has sufficient time to target the tumor before administering a small, fast-clearing radiolabeled complementary PNA that hybridizes with the antibody-PNA conjugate at the tumor side. Rapid clearance of the radiolabeled PNA significantly reduces radiation exposure of non-target tissues and its small size permits speedy delivery to the tumor, creating excellent tumor/non-tumor ratios. These appealing characteristics allow the rational application of the pretargeting approach for diagnosis as well as therapy of cancer.
Herein a successful tumor pretargeting approach using PNA radiolabeled with clinically available 99mTc and complementary PNA linked to the antibody Cetuximab in murine xenografts will be presented. Importantly, no metabolization and a high specific tumor accumulation of the PNA conjugate were observed.
The results presented in this work are promising in the view of further preclinical studies including internal radiotherapeutic treatment.
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Vortrag (Konferenzbeitrag)
PACIFICHEM 2015, 15.-20.12.2015, Honolulu, USA
Permalink: https://www.hzdr.de/publications/Publ-23104