Comparison of 99m Tc-UBI 29-41, 99m Tc-ciprofloxacin, 99m Tc-ciprofloxacin dithiocarbamate and 111In-biotin for targeting experimental staphylococcus aureus and escherichia coli foreign-body infections. an ex-vivo study

BACKGROUND: Diagnosis of implant-associated infection is challenging. Several radiopharmaceuticals have been described but direct comparisons are limited. Here we compared in vitro and in an animal model Tc-99m-IJIBI, Tc-99m-cipmfloxacin, (TcN)-Tc-99m-CipmCS(2) and In-111-DTPA-biotin for targeting E. coli (ATCC 25922) and S. aureus (ATCC 43335).METHODS: Stability controls were performed with the labelled radiopharmaceuticals during 6 hours in saline and serum. The in vitro binding to viable or killed bacteria was evaluated at 37 degrees C and 4 degrees C. For in vivo studies, Teflon cages were subcutaneously implanted in mice, followed by percutaneous infection. Biodistribution of i.v. injected radiolabelled radiopharmaceuticals were evaluated during 24 h in cages and dissected tissues.RESULTS: Labelling efficiency of all radiopharmaceuticals ranged between 94% and 98%, with high stability both in saline and in human serum. In vitro binding assays displayed a rapid but poor bacterial binding for all tested agents. Similar binding kinetic occurred also with heat-killed and ethanol-killed bacteria. In the tissue cage model, infection was detected at different time points: Tc-99m-UBI and (TcN)-Tc-99m-CiproCS(2) shoved higher infected cage/sterile cage ratio at 24 hours for both E. coli and S. aureus; Tc-99m-Ciprofloxacin at 24 hours for both E. coli and at 4 hours for S. aureus; In-111-DTPA-biotin accumulates faster in both E. coli and S. aureus infected cages.CONCLUSIONS: Tc-99m-UBI, (TeN)-Te-99m-CiproCS(2) showed poor in vitro binding but good in vivo binding to E. coli only. In-111-DTPA-biotin showed poor in vitro binding but good in vivo binding to S. aureus and poor to E. coli. Tc-99m-Ciprofloxacin showed poor in vitro binding but good in vivo binding to all tested bacteria. The mechanism of accumulation in infected sites remains to be elucidated.