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^99mTc-Labeled UBI 29-41 Peptide for Monitoring the Efficacy of Antibacterial Agents in Mice Infected with Staphylococcus aureus

¹ Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands
² Division of Nuclear Medicine, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands
³ AM-Pharma, Bunnik, The Netherlands
⁴ Dipartimento di Patologia Sperimentale, Biotecnologie Mediche, Infettivologia ed Epidemiologia, Università degli Studi di Pisa, Pisa, Italy

View larger version (19K): [in a new window]   FIGURE 1. (A) Mice infected with S. aureus were injected subcutaneously with various doses of cloxacillin. Accumulation of 99mTc-UBI 29-41 in the infected thigh muscles of untreated (open bars) mice or animals treated with 5 mg/kg (closed bars), 50 mg/kg (horizontally hatched bars), or 500 mg/kg (diagonally hatched bars) cloxacillin is expressed as T/NT (plus SEM) of at least 4 mice. (B) Mice infected with S. aureus were injected subcutaneously with erythromycin. Accumulation of 99mTc-UBI 29-41 in the infected thigh muscles of untreated (open bars) mice or animals treated with 10 mg/kg erythromycin (closed bars) is expressed as T/NT (plus SEM) of at least 4 mice. (C) Rats infected with antibiotic-resistant S. aureus were injected intravenously with various doses of hLF 1-11. Accumulation of 99mTc-UBI 29-41 in the infected thigh muscles of untreated (open bars) rats or animals treated with 4 µg/kg (closed bars) or 40 µg/kg (horizontally hatched bars) hLF 1-11 is expressed as T/NT (plus SEM) of at least 4 rats. *Values that were significantly (P < 0.05) different from those in untreated rats.

View larger version (14K): [in a new window]   FIGURE 2. Effect of various doses of cloxacillin (A), erythromycin (B), and hLF 1-11 (C) on the number of viable bacteria in animals infected with S. aureus or antibiotic-resistant S. aureus. Values are means (plus SEM) CFU per gram of thigh muscle at 24 h after injection of the antibacterial agent (n > 4 for each bar). *Values significantly different from those in untreated animals.

View larger version (50K): [in a new window]   FIGURE 3. Typical scintigrams of mice with S. aureus infection (A–C) intravenously injected with 2–7 MBq 99mTc-UBI 29-41 after treatment with 50 mg/kg cloxacillin (B), 10 mg/kg erythromycin (C), or no antibiotic (A). In addition, typical scintigrams of rats with antibiotic-resistant S. aureus infection (D and E) intravenously injected with 2–7 MBq 99mTc-UBI 29-41 after treatment with 40 µg/kg hLF 1-11 (E) or no peptide (D). Arrows indicate the infected thigh muscle.