Preparation, Quality Control and Biological Evaluation of Tc-99m-Clarithromycin in Animal Models for Detection of Bacterial Infection

Clarithromycin is a macrolide antibiotic effective against bacteria by interfering their protein synthesis. In the present investigation, Tc-99m-clarithromycin as a promising radiopharmaceutical for detecting staphylococcus aureus infection imaging in nuclear medicine is evaluated. At pH 7, clarithromycin was labelled with Tc-99m with a labelling yield of 99% by adding Tc-99m to 500 mu g of clarithromycin in the presence of 25 mu g using stannous chloride as reducing agent at room temperature. Radiochemical purity of the compound was analyzed by ascending chromatographic techniques and HPLC analysis. Electrophoresis indicates the neutral behavior of Tc-99m-clarithromycin. HPLC analysis confirms the single species of the Tc-99m-clarithromycin complex. Biodistribution of Tc-99m-clarithromycin was evaluated in animal models by inducing infection using live S. aureus, heat killed S. aureus, and turpentine oil (sterile inflammation model) which showed high uptake in infection induced sites (live S. aureus). Bio-evaluation by scintigraphic imaging also revealed high uptake of Tc-99m-clarithromycin at S. aureus infected sites. Biodistribution and scintigraphic imaging of Tc-99m-clarithromycin in infected mice and rabbit showed a good target-to- non target ratio indicating it a possible bacterial infection imaging agent.