Radiopharmaceutical Evaluation of Peptide Nucleic Acid Bioconjugates as Complementary System for Tumor Targeting

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.