Preparation and Evaluation of a Novel ^99mTc-Labeled Niraparib Isonitrile Complex as a Potential PARP-1 Imaging Agent

Abstract

Poly ADP-ribose polymerase (PARP) plays an important role in the DNA repair process and has become an attractive target for cancer therapy in recent years. Given that niraparib has good clinical efficacy as a PARP inhibitor, this study aimed to develop radiolabeled niraparib derivatives for tumor imaging to detect PARP expression and improve the accuracy of stratified patient therapy. The niraparib isonitrile derivative (CNPN) was designed, synthesized, and radiolabeled to obtain the [ 99m Tc]Tc-CNPN complex with high radiochemical purity (>95%). It was lipophilic and stable in vitro. In HeLa cell experiments, the uptake of [ 99m Tc]Tc-CNPN was effectively inhibited by the ligand CNPN, indicating the binding affinity for PARP. According to the biodistribution studies of HeLa tumorbearing mice, [ 99m Tc]Tc-CNPN has moderate tumor uptake and can be effectively inhibited, demonstrating its specificity for targeting PARP. The SPECT imaging results showed that [ 99m Tc]Tc-CNPN had tumor uptake at 2 h postinjection. All of the results of this study indicated that [ 99m Tc]Tc-CNPN is a promising tumor imaging agent that targets PARP.