title: ⁶⁸Ga-NOTA-UBI-29-41 as a PET Tracer for Detection of Bacterial Infection.
abstract: The cationic peptide (68)Ga-NOTA-UBI-29-41 was synthesized and characterized. Biodistribution and PET/CT examinations were performed for evaluation of its biologic behavior. Differentiation of infection from sterile inflammation was investigated using microbiology methods at the sites of bacterial infections.
  
  
  METHODS
  Labeling of UBI-29-41 conjugated with NOTA with (68)Ga was optimized at 20°C-100°C and pH 3.5-5.5. Radiochemical purity, stability up to 260 min, and binding to serum proteins were determined. In vitro binding to Staphylococcus aureus was evaluated from 9.14 × 10(7) to 1.17 × 10(10) cfu/mL. Of 3 groups of Mus musculus Swiss male mice, the first was inoculated intramuscularly with 1.2 × 10(8) cfu of S. aureus to provoke infection, and the second, with 1.2 × 10(8) cfu of heat shock-treated S. aureus to generate sterile inflammation. The third mouse was not treated and served as a control. After 24 h, (68)Ga-NOTA-UBI-29-41 was administrated intravenously, and biodistribution was performed at 30, 60, and 120 min. PET/CT dynamic studies (120 min) were acquired. Sinograms were reconstructed using 3D maximum-likelihood expectation maximization and analyzed with software. Infected or inflamed muscles were dissected, homogenized, and cultured in tryptic soy agar medium. Recovered S. aureus was calculated as cfu/g.
  
  
  RESULTS
  (68)Ga-NOTA-UBI-29-41 showed high renal excretion (83.2% ± 7.3%) of injected dose and rapid blood clearance. More than 95% was bound in vitro to 5 × 10(9) cfu/mL. A significantly higher (P< 0.05) accumulation of (68)Ga-NOTA-UBI-29-41 was observed at sites of S. aureus inoculation in infected mice (ratio of target to nontarget, 5.0 at 60 min and 4.1 at 120 min) compared with animals with inflammation (ratio of target to nontarget, 1.6 at 60 min and 1.2 at 120 min).
  
  
  CONCLUSIONS
  The difference in uptake of (68)Ga-NOTA-UBI-29-41 in the infected muscles compared with the inflamed muscles was clearly observed in the PET/CT images and positively correlated with the degree of infection.
authors.affiliation: Uruguayan Centre of Molecular Imaging, Montevideo, Uruguay vilcheclaps@gmail.com.
authors.forename: Mónica
authors.initials: M
authors.lastname: Vilche
authors.affiliation: Uruguayan Centre of Molecular Imaging, Montevideo, Uruguay.
authors.forename: Ana Laura
authors.initials: AL
authors.lastname: Reyes
authors.affiliation: Uruguayan Centre of Molecular Imaging, Montevideo, Uruguay.
authors.forename: Elena
authors.initials: E
authors.lastname: Vasilskis
authors.affiliation: Uruguayan Centre of Molecular Imaging, Montevideo, Uruguay.
authors.forename: Patricia
authors.initials: P
authors.lastname: Oliver
authors.affiliation: Uruguayan Centre of Molecular Imaging, Montevideo, Uruguay.
authors.forename: Henia
authors.initials: H
authors.lastname: Balter
authors.affiliation: Uruguayan Centre of Molecular Imaging, Montevideo, Uruguay.
authors.forename: Henry
authors.initials: H
authors.lastname: Engler
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D001424:Bacterial Infections / Q000000981:diagnostic imaging* / Q000382:microbiology; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000493:pharmacokinetics; D007249:Inflammation / Q000000981:diagnostic imaging; D007553:Isotope Labeling / Q000379:methods; D008297:Male; D051379:Mice; D010455:Peptides / Q000138:chemical synthesis / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography / Q000379:methods*; D011485:Protein Binding; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D013203:Staphylococcal Infections / Q000000981:diagnostic imaging; D014018:Tissue Distribution
chemical_list: C000609786:68Ga-NOTA-UBI-29-41; D056831:Coordination Complexes; D010455:Peptides; D019275:Radiopharmaceuticals
keywords: 68Ga; PET/CT; UBI-29-41; infection diagnosis; ubiquicidin-derived peptide