Radionuclide therapy of bevacizumab-based PNA-mediated pretargeting

Background The radionuclide-labeled bevacizumab (BV) is a potential therapeutic approach for vascular endothelial growth factor overexpressed tumors. Because of its large molecular weight, BV is cleared slowly in vivo , which caused damage to healthy tissues and organs. On account of this situation, using the pretargeting strategy with DNA/RNA analogs, such as peptide nucleic acid (PNA), is an effective way of treating solid tumors. Methods The BV-PNA conjugate (BV-PNA-1) was injected intravenously as the pretargeted probe, which was specifically accumulated in a solid tumor and gradually metabolically cleared. Then the 177 LuLu-labeled complementary PNA strand ( 177 LuLu-PNA-2) as the second probe was injected, and bound with BV-PNA-1 by the base complementary pairing. In this study, the BV-based PNA-mediated pretargeting strategy was systematically studied, including stability of probes, specific binding ability, biodistribution in animal model, evaluation of single photon emission computed tomography/computed tomography imaging, and therapeutic effect. Results Compared with group A ( 177 LuLu-BV), the group B (BV-PNA-1 + 177 LuLu-PNA-2) showed lower blood radiotoxicity (22.55 ±1.62 vs. 5.18 ± 0.40%, %ID/g, P 0.05). Correspondingly, there was no significant difference in therapeutic effect between groups A and B. Conclusion The PNA-mediated pretargeting strategy could increase the tumor-to-blood ratio, thereby reducing the damage to normal tissues, while having a similar therapeutic effect to solid tumor. All the experiments in this study showed the potential and effectiveness of pretargeting radioimmunotherapy.