In vitro and in vivo assessment of 99mTc-UBI specificity for bacteria

Technetium-99m labeled ubiquicidin peptide 29-41 (Tc-99m-UBI) is a cationic human antimicrobial peptide fragment that has been shown to bind bacteria in vitro and accumulates at sites of infection in experimental animals. To help determine if Tc-99m-UBI is bound to the bacterial cell envelope by a simple nonspecific electrostatic interaction, a comparative study of the in vitro binding of Tc-99m-UBI and two different Tc-99m labeled cationic peptides (Tc-99m-Tat-1-Scr and Tc-99m-Tat-2-Scr) to bacteria and to two tumor cell line (LS174T and ACHN) was performed. The in vivo specificity of Tc-99m-UBI for infection in mice was also evaluated using dual labels in the same animal and comparing the target/non-target ratio for Ga-67-citrate and Tc-99m-UBI at sites of induced infection and sterile inflammation. Under conditions of this study, the in vitro binding of Tc-99m-UBI, Tc-99m-Tat-1-Scr and Tc-99m-Tat-2-Scr to S. aureus was 35, 78 and 87% respectively. While the binding of Tc-99m-Tat-1-Scr and Tc-99m-Tat-2-Scr was 37 and 33% to colon tumor cells (LS174T) and 39 and 41% to renal tumor cells (ACHN) respectively, the binding of Tc-99m-UBI to both cell types was much lower at less than 4%. In vivo studies revealed that there is a significant difference (p < 0.05) in the radioactive accumulation of Tc-99m-UBI between the sites of infection and inflammation compared to Ga-67-citrate. Thus, Tc-99m-UBI showed an average infection/inflammation ratio of 2.08 +/- 0.49 compared to 1.14 +/- 0.45 for Ga-67-citrate. In conclusion, the in vitro and in vivo results provide evidence that a specific mechanism is responsible of the Tc-99m-UBI bacterial intracellular accumulation. (C) 2003 Elsevier Inc. All rights reserved.