99mTc-labeled antimicrobial peptide ubiquicidin (29-41) accumulates less in Escherichia coli infection than in Staphlococcus aureus infection

Abstract

99mTc-Labeled antimicrobial peptide ubiquicidin, (99m)Tc-UBI (29-41) in a freeze-dried kit, was evaluated as a bacterial infection-seeking agent in Staphlococcus aureus- and Escherichia coli-induced infections.

Methods: Thirty-three rabbits were classified in 3 groups. Biodistribution of (99m)Tc-UBI (29-41) was studied in 3 animals (group I). Uptake of peptide was determined by counting radioactivity in anatomically fitted regions drawn over the liver, kidneys, urinary bladder, and whole body and expressed as the percentage uptake per organ. Experimental thigh muscle infection was induced by injecting 2 x 10(8) colony-forming units of live S. aureus or E. coli bacteria into the right thigh muscle in 20 rabbits (group II). Turpentine oil and formalin-killed S. aureus were used for inducing sterile thigh muscle inflammation in 10 rabbits (group III). On scintigrams, anatomically adjusted regions of interest were drawn over infected/inflamed (target) and noninfected/noninflamed (nontarget) thigh, and accumulation of (99m)Tc-UBI (29-41) at sites of infection/inflammation was expressed as a target-to-nontarget (T/NT) ratio.

Results: A biodistribution study of (99m)Tc-UBI (29-41) revealed rapid removal of tracer from the circulation via the kidneys (10.6% +/- 2.1% at 5 min and 5.9% +/- 0.8% at 60 min) with accumulation of the major part in the urinary bladder within the first hour after injection (66.6% +/- 7.2%). A significantly higher (P < 0.05) accumulation of (99m)Tc-UBI (29-41) was seen at sites of S. aureus-infected animals (T/NT ratio, 2.2 +/- 0.5) compared with that of E. coli-infected animals (T/NT ratio, 1.7 +/- 0.4). The maximum tracer accumulation was observed at 60 min after injection followed by a gradual decline. No significant accumulation was noticed in thighs of rabbits injected with either turpentine oil or killed S. aureus with markedly lower T/NT ratios (P < 0.05) compared with that of S. aureus- and E. coli-infected thighs.

Conclusion: A (99m)Tc-UBI (29-41) freeze-dried kit can be used for differentiating infections with S. aureus and E. coli with significantly higher scintigraphic intensity (P < 0.05) compared with that of sterile inflammatory sites. The optimum time for infection imaging is 60 min after injection. Relatively low (T/NT) ratios were observed in E. coli infections compared with those of the S. aureus group, which may be due to a low virulence of the former; however, other possible reasons may include low affinity of this peptide for E. coli microbial membranes.