Synthesis and biological evaluation of a novel 99mTc(CO)3 complex of ciprofloxacin dithiocarbamate as a potential agent to target infection.

Abstract

The ciprofloxacin dithiocarbamate (CPFXDTC) was radiolabeled with [(99m)Tc(CO)(3)(H(2)O)(3)](+) intermediate to form the (99m)Tc(CO)(3)-CPFXDTC complex in high yield. The (99m)Tc(CO)(3)-CPFXDTC complex was characterized by HPLC and its stability in serum was studied. Its partition coefficient indicated that it was a lipophilic complex. The bacterial binding efficiency of (99m)Tc(CO)(3)-CPFXDTC was almost the same as that of (99m)TcN-CPFXDTC, and was higher than that of (99m)Tc-ciprofloxacin. Biodistribution results in induced infection mice showed (99m)Tc(CO)(3)-CPFXDTC had higher uptake at the sites of infection and better abscess/blood and abscess/muscle ratios than those of (99m)Tc-ciprofloxacin and (99m)TcN-CPFXDTC. Single photon emission computed tomography (SPECT) static imaging study in infected rabbits demonstrated the uptake in the left thigh infection lesion was observable, while no accumulation in the right thigh muscle was found. These results suggested (99m)Tc(CO)(3)-CPFXDTC would be a promising candidate for further evaluation as infection imaging agent.

• Authors: Junbo Zhang, Shijian Zhang, Haixun Guo, Xuebin Wang
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 20 Issue 12 Pg. 3781-4 (Jun 15 2010) ISSN: 1464-3405 [Electronic] England
• PMID: 20471828 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 Elsevier Ltd. All rights reserved.

Chemical References

• Organotechnetium Compounds
• Radiopharmaceuticals
• Thiocarbamates
• ciprofloxacin dithiocarbamate
• Ciprofloxacin

Topics

• Animals
• Bacterial Adhesion
• Blood (microbiology)
• Ciprofloxacin (analogs & derivatives, chemical synthesis)
• Drug Stability
• Infections (diagnosis, pathology)
• Mice
• Muscle, Skeletal (microbiology)
• Organotechnetium Compounds (chemical synthesis)
• Rabbits
• Radiopharmaceuticals (chemical synthesis)
• Thiocarbamates (chemical synthesis)
• Tissue Distribution
• Tomography, Emission-Computed, Single-Photon (methods)