Development of Novel 99mTc-Labeled Hydrazinoicotinamide-Modified Ubiquicidin 29-41 Complexes with Improved Target-to-Nontarget Ratios for Bacterial Infection Imaging.

Abstract

To develop novel ^99mTc-labeled ubiquicidin 29-41 derivatives for bacterial infection SPECT imaging aiming at achieving a high target-to-nontarget ratio and lower nontarget organ uptake, a novel 6-hydrazinoicotinamide (HYNIC) ubiquicidin 29-41 derivative (HYNIC-UBI 29-41) was designed and synthesized. It was then radiolabeled with ternary ligands, including TPPTS, PDA, 2,6-PDA, NIC, ISONIC, PSA, 4-PSA, and PES, to obtain eight ^99mTc-labeled HYNIC-UBI 29-41 complexes. All the complexes demonstrated hydrophilicity, exhibited good in vitro stability, and specifically bound Staphylococcus aureus in vitro. Biodistribution studies in mice with bacterial infection demonstrated that [^99mTc]Tc-tricine/TPPTS-HYNIC-UBI 29-41 resulted in increased abscess-to-muscle and abscess-to-blood ratios as well as decreased nontarget organ uptake. Furthermore, it was able to distinguish between bacterial infection and sterile inflammation. Single-photon emission computed tomography (SPECT) imaging studies in mice with bacterial infection revealed visible accumulation at the site of infection, indicating that [^99mTc]Tc-tricine/TPPTS-HYNIC-UBI 29-41 is a potential radiotracer for imaging bacterial infection.