Synthesis, biological evaluation and biodistribution of the 99mTc–Garenoxacin complex in artificially infected rats

Abstract

The labeling of garenoxacin (GXN) with technetium-99m (99mTc) using different concentrations of GXN, sodium pertechnetate (Na99mTcO4), stannous chloride dihydrate (SnCl2·2H2O) at different pH was investigated and evaluated in terms of in-vitro stability in saline, serum, binding with multi-resistant Staphylococcus aureus (MDRSA) and penicillin-resistant Streptococci (PRSC) and its biodistribution in artificially MDRSA and PRSC infected rats. 99mTc–GXN complex with 97.45 ± 0.18% radiochemical stability was prepared by mixing 3 mg of GXN with 3 mCi of Na99mTcO4 in the presence of 150 μL of SnCl2·2H2O (1 μg/μL in 0.01 N HCl) at a pH 5.6. The radiochemical stability of the complex was evaluated in normal saline up to 240 min of reconstitution. It was observed that the complex showed maximum RCP values after 30 min of the reconstitution and remained more than 90% up to 240 min. The complex showed radiochemical stability in normal saline at 37 °C up to 16 h with a 17.80% de-tagging. The complex showed saturated in-vitro binding with living MDRSA and PRSC as compared to the insignificant binding with heat killed MDRSA and PRSC. Biodistribution behavior of the complex was assessed in artificially infected with living and heat killed MDRSA and PRSC rats. It was observed that the accumulation of the complex in the infected (live MDRSA and PRSC) tissue of the rats was almost five fold than in the inflamed and normal tissue. The high radiochemical stability in normal saline at room temperature, promising in-vitro stability in serum at 37 °C, saturated in-vitro binding with living MDRSA and PRSC, specific biodistribution behavior and high infected (target) to normal (non-target) tissue and low inflamed (non-target) to normal (non-target) tissue ratios we recommend 99mTc–GXN complex for in-vivo localization of infection caused by MDRSA and PRSC effective stains.