Synthesis and Evaluation of Novel Norfloxacin Isonitrile 99mTc Complexes as Potential Bacterial Infection Imaging Agents

Abstract

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

Synthesis and Bioevaluation of Novel Technetium-99m-Labeled Complexes with Norfloxacin HYNIC Derivatives for Bacterial Infection Imaging

“…To verify that the biodistribution properties of the 99m Tc-labeled norfloxacin HYNIC derivative can be improved, the partition coefficient and biological properties of 99m TcN-NFXDTC, [ 99m Tc]­Tc-CN5NF, and [ 99m Tc]­Tc-EDDA-HYNICNF were compared and analyzed. As reported in ref and , the partition coefficients of 99m TcN-NFXDTC, [ 99m Tc]­Tc-CN5NF, and [ 99m Tc]­Tc-EDDA-HYNICNF were 1.02, −1.75 ± 0.03, and −1.33 ± 0.05, respectively. According to the partition coefficients, 99m TcN-NFXDTC was lipophilic, while [ 99m Tc]­Tc-CN5NF and [ 99m Tc]­Tc-EDDA-HYNICNF were hydrophilic.…”

“…The retention times of [ 99m Tc]­Tc-tricine-TPPTS-HYNICNF, [ 99m Tc]­Tc-tricine-TPPMS-HYNICNF, and [ 99m Tc]­Tc-EDDA-HYNICNF were 9.54, 15.32, and 9.58 min, respectively. Under the same conditions, the retention time of [ 99m Tc]­TcO 4 – was 3.93 min . The HPLC analysis results showed that the RCPs of the radiotracers were greater than 95%.…”

“…Under the same conditions, the retention time of [ 99m Tc]TcO 4 − was 3.93 min. 21 The HPLC analysis results showed that the RCPs of the radiotracers were greater than 95%.…”

“…We have reported 99m TcNlabeled norfloxacin dithiocarbamate derivatives in 2011 20 and 99m Tc-labeled norfloxacin isonitrile derivatives in 2021. 21 Both complexes can specifically bind bacteria in vitro and bacterial infection sites in vivo and distinguish them from sterile inflammation. However, these two bacteria-specific imaging agents have a high radioactivity concentration in the liver, which affects the imaging quality.…”

“…Norfloxacin can be modified with different chelating groups to obtain different types of norfloxacin derivatives that can coordinate with technetium-99m. We have reported 99m TcN-labeled norfloxacin dithiocarbamate derivatives in 2011 and 99m Tc-labeled norfloxacin isonitrile derivatives in 2021 . Both complexes can specifically bind bacteria in vitro and bacterial infection sites in vivo and distinguish them from sterile inflammation.…”