期刊
CHEMICAL SCIENCE
卷 6, 期 10, 页码 5601-5616出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/c5sc00951k
关键词
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资金
- Swiss National Science Foundation [PP00P2_133568133568, PP00P2PP00P2_157545157545, 200021_129910, 200020_146776]
- University of Zurich
- Stiftung fur Wissenschaftliche Forschung of University of Zurich
- Helmholtz Virtual Institute NanoTracking [VH-VI-421]
- Research Department Interfacial Systems Chemistry at Ruhr University Bochum
- COST Action CM1105
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 Tc-99m-labeled PNA. In vivo studies on tumor bearing mice demonstrated a rapid and efficient in vivo hybridization of the radiolabeled PNA with the antibodyPNA 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).
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