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

摘要: A novel, promising strategy for cancer diagnosis and therapy is the use of a pretargeting approach. For this purpose, non-natural DNA/RNA analogues Peptide Nucleic Acids (PNAs) are ideal candidates as in vivo recognition units due to their high metabolic stability lack unspecific accumulation. In approach, an unlabeled, highly specific antibody–PNA conjugate has sufficient time target tumor before administration small fast-clearing radiolabeled complementary PNA that hybridizes with at site. Herein, we report first successful application multistep process using PNA-modified epidermal growth factor receptor (EGFR) antibody (cetuximab) 99mTc-labeled PNA. studies on bearing mice demonstrated rapid efficient hybridization conjugate. Decisively, accumulation was observed tumor-to-muscle ratio >8, resulting clear visualization by single photon emission computed tomography (SPECT).