Synthesis and Evaluation of Novel Norfloxacin Isonitrile (99m)Tc Complexes as Potential Bacterial Infection Imaging Agents

To develop potential technetium-99m single-photon emission computed tomography (SPECT) imaging agents for bacterial infection imaging, the novel norfloxacin isonitrile derivatives CN4NF and CN5NF were synthesized and radiolabeled with a [(99m)Tc][Tc(I)](+) core to obtain [(99m)Tc]Tc-CN4NF and [(99m)Tc]Tc-CN5NF. These compounds were produced in high radiolabeling yields and showed hydrophilicity and good stability in vitro. The bacterial binding assay indicated that [(99m)Tc]Tc-CN4NF and [(99m)Tc]Tc-CN5NF were specific to bacteria. Compared with [(99m)Tc]Tc-CN4NF, biodistribution studies of [(99m)Tc]Tc-CN5NF showed a higher uptake in bacteria-infected tissues than in turpentine-induced abscesses, indicating that [(99m)Tc]Tc-CN5NF could distinguish bacterial infection from sterile inflammation. In addition, [(99m)Tc]Tc-CN5NF had higher abscess/blood and abscess/muscle ratios. SPECT image of [(99m)Tc]Tc-CN5NF showed that there was a clear accumulation in the infection site, suggesting that it could be a potential bacterial infection imaging radiotracer.