99mTc(CO)3–Garenoxacin dithiocarbamate synthesis and biological evolution in rats infected with multiresistant Staphylococcus aureus and penicillin-resistant Streptococci

Abstract

99mTc(CO)3–Garenoxacin dithiocarbamate (99mTc(CO)3–GXND) complex was synthesized and biologically characterized in rats artificially infected with multiresistant Staphylococcus aureus (MDRSA) and penicillin-resistant Streptococci (PRSC). The characteristics of the 99mTc(CO)3–GXND complex was assessed in terms of radiochemical stability in saline, serum, in vitro binding with live and heat killed MDRSA and PRSC and biodistribution in rats artificially infected with MDRSA and PRSC. The complex showed maximum radiochemical stability at 30 min and remained more than 90% stable up to 240 min in normal saline after reconstitution. The complex was found stable in serum at 37 °C up to 16 h. The complex showed in vitro saturated binding with living MDRSA and PRSC. In rats infected with living MDRSA and PRSC the complex showed five higher up take in the infected muscle as compared to the inflamed and normal muscle. No significant difference in uptake of the complex in rats infected with heat killed MDRSA and PRSC was observed. The disappearance of the complex from the blood and appearance in the urinary system confirm the normal biological route of biodistribution and excretion. The high values of the radiochemical stability in normal saline, serum, saturated in vitro binding with living MDRSA and PRSC and significant infected to normal muscles ratios, the 99mTc(CO)3–GXND complex is recommended for the localization of soft tissue infection caused by living MDRSA and PRSC.