In vitro and in vivo assessment of 99mTc-UBI specificity for bacteria.
Technetium-99m labeled ubiquicidin peptide 29-41 ((99m)Tc-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 (99m)Tc-UBI is bound to the bacterial cell envelope by a simple nonspecific electrostatic interaction, a comparative study of the in vitro binding of (99m)Tc-UBI and two different (99m)Tc labeled cationic peptides ((99m)Tc-Tat-1-Scr and (99m)Tc-Tat-2-Scr) to bacteria and to two tumor cell line (LS174T and ACHN) was performed. The in vivo specificity of (99m)Tc-UBI for infection in mice was also evaluated using dual labels in the same animal and comparing the target/non-target ratio for (67)Ga-citrate and (99m)Tc-UBI at sites of induced infection and sterile inflammation. Under conditions of this study, the in vitro binding of (99m)Tc-UBI, (99m)Tc-Tat-1-Scr and (99m)Tc-Tat-2-Scr to S. aureus was 35, 78 and 87% respectively. While the binding of (99m)Tc-Tat-1-Scr and (99m)Tc-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 (99m)Tc-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 (99m)Tc-UBI between the sites of infection and inflammation compared to (67)Ga-citrate. Thus, (99m)Tc-UBI showed an average infection/inflammation ratio of 2.08 +/- 0.49 compared to 1.14 +/- 0.45 for (67)Ga-citrate. In conclusion, the in vitro and in vivo results provide evidence that a specific mechanism is responsible of the (99m)Tc-UBI bacterial intracellular accumulation.
Ferro-Flores
Guillermina
G
Instituto Nacional de Investigaciones Nucleares, México, Mexico. gff@nuclear.inin.mx
Arteaga de Murphy
Consuelo
C
Pedraza-López
Martha
M
Meléndez-Alafort
Laura
L
Zhang
Yu-Min
YM
Rusckowski
Mary
M
Hnatowich
Donald J
DJ
D000818:Animals; D002292:Carcinoma, Renal Cell / Q000000981:diagnostic imaging* / Q000378:metabolism*; D045744:Cell Line, Tumor; D002951:Citrates / Q000493:pharmacokinetics; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005708:Gallium / Q000493:pharmacokinetics; D006801:Humans; D007680:Kidney Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism; D051379:Mice; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics*; D010446:Peptide Fragments / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013203:Staphylococcal Infections / Q000000981:diagnostic imaging* / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000302:isolation & purification / Q000378:metabolism*
D002951:Citrates; D015609:Organotechnetium Compounds; D010446:Peptide Fragments; D019275:Radiopharmaceuticals; C485080:technetium 99m ubiquicidin(29-41); D005708:Gallium; C103850:gallium citrate