99mTc-labeling of ciprofloxacin and nitrofuryl thiosemicarbazone using fac-[99mTc(CO)₃(H₂O)₃] core: evaluation of their efficacy as infection imaging agents

摘要

The aim of this study was to radiolabel ciprofloxacin (Cip) and nitrofuryl thiosemicarbazone (NFT) with the fac-[99mTc(CO)₃(H₂O)₃]+ core and to evaluate the ability of the radiopharmaceuticals as tracers in detecting sites of infection. Cip and NFT were radiolabeled with the fac-[99mTc(CO)₃(H₂O)₃]+ core and characterized by RHPLC. The stabilities of the preparations were evaluated in saline and rat serum. In vitro binding studies of the radiopharmaceuticals with S. aureus were performed. Biodistribution studies were conducted at different time points after injecting (i.v.) the radiopharmaceuticals in rats (intramuscularly infected with S. aureus) as well as in rats with sterile inflammation. To assess the infection targeting capacity of 99mTc-tricarbonyl ciprofloxacin and nitrofuryl thiosemicarbazone, 99mTc(V)O-Cip and 99mTc(V)O-NFT were used as control. Scintigraphic imaging studies of tricarbonyl compounds and 99mTc(V)O-Cip were performed at 4 h after injection. The radiochemical purities of 99mTc(CO)₃-Cip and 99mTc(CO)₃-NFT were between 97–98% as determined by thin layer chromatography (TLRC) and RHPLC; no further purification is necessary before injection. The radiopharmaceuticals exhibited substantial stability when incubated in isotonic saline and serum up to 24 h. Biodistribution studies showed maximum uptake in the infected rat thigh muscle at 4 h post injection and washing out at slower rate from the infected site than the oxo technetium chelate. The mean ratios of uptake in infectedon–infected thighs were 3.87:1, 3.41:1 and 3.17:1 for 99mTc(CO)₃-Cip, 99mTc(CO)₃-NFT and 99mTc(V)O-Cip respectively. During scintigraphic studies, infection sites appeared quite distinctly with 99mTc(CO)₃-Cip and 99mTc(CO)₃-NFT, comparable to the behaviour with 99mTc(V)O-Cip. These results encouraged us for further development of infection imaging radiopharmaceuticals based on the 99mTc-tricarbonyl core.