title: Identification of Staphylococcus aureus infection by aptamers directly radiolabeled with technetium-99m.
abstract: BACKGROUND
  Aptamers are oligonucleotides that have high affinity and specificity for their molecular targets which are emerging as a new class of molecules for radiopharmaceuticals development. In this study, aptamers selected to Staphylococcus aureus were evaluated for bacterial infection identification.
  
  
  METHODS
  Anti S. aureus aptamers were labeled with (99m)Tc by the direct method. The radiolabel yield and complex stability were assessed by thin-layer chromatography (TLC). Three groups of Swiss mice containing 6 animals each were used. The first group was infected intramuscularly in the right thigh with S. aureus. The second group was infected in the same way with C. albicans and the third group was injected with zymosan to induce aseptic inflammation. After 24 h, radiolabeled aptamers (22.2 MBq) were injected by the tail vein. The mice were euthanized 4 h post injection and tissue sample activities measured in a gamma counter.
  
  
  RESULTS
  The (99m)Tc labeled aptamers were stable in saline, plasma and cystein excess. Radiolabeled aptamers showed increased uptake in the kidneys for all groups indicating a main renal excretion, which is consistent with the hydrophilic nature and small size of aptamers. The radiopharmaceutical showed rapid blood clearance indicated by a reduced dose (% ID/g) in the blood. The biodistribution showed that aptamers were able to identify the infection foci caused by S. aureus displaying a target/non-target ratio of 4.0±0.5. This ratio for mice infected with C. albicans was 2.0±0.4 while for mice with aseptic inflammation was 1.2±0.2. Histology confirmed the presence of infection in groups 1 and 2, and inflammation in group 3.
  
  
  CONCLUSIONS
  The biodistibution study demonstrated a statistically higher uptake in the S. aureus foci relative to inflammation and C. albicans infected areas. These results highlight the potential of aptamers labeled directly with (99m)Tc for bacterial infection diagnosis by scintigraphy.
authors.affiliation: Centro de Desenvolvimento da Tecnologia Nuclear (CDTN), Rua Professor Mário Werneck S/N°, Cidade Universitária, Campus da UFMG, 31120-970, Belo Horizonte, MG, Brasil. Electronic address: sararoberta7@hotmail.com.
authors.forename: Sara Roberta
authors.initials: SR
authors.lastname: dos Santos
authors.affiliation: Centro de Desenvolvimento da Tecnologia Nuclear (CDTN), Rua Professor Mário Werneck S/N°, Cidade Universitária, Campus da UFMG, 31120-970, Belo Horizonte, MG, Brasil. Electronic address: crisrcorrea@gmail.com.
authors.forename: Cristiane
authors.initials: C
authors.lastname: Rodrigues Corrêa
authors.affiliation: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Cidade Universitária, Campus da UFMG, 31270-091, Belo Horizonte, MG, Brazil. Electronic address: brancodebarros@yahoo.com.br.
authors.forename: André Luís
authors.initials: AL
authors.lastname: Branco de Barros
authors.affiliation: Departamento de Clinica e Cirurgia, Escola de Veterinária, Universidade Federal de Minas Gerais, Cidade Universitária, Campus da UFMG, 31270-091, Belo Horizonte, MG, Brazil. Electronic address: serakidesufmg@gmail.com.
authors.forename: Rogéria
authors.initials: R
authors.lastname: Serakides
authors.affiliation: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Cidade Universitária, Campus da UFMG, 31270-091, Belo Horizonte, MG, Brazil. Electronic address: simone@farmacia.ufmg.br.
authors.forename: Simone Odília
authors.initials: SO
authors.lastname: Fernandes
authors.affiliation: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Cidade Universitária, Campus da UFMG, 31270-091, Belo Horizonte, MG, Brazil. Electronic address: cardosov@farmacia.ufmg.br.
authors.forename: Valbert Nascimento
authors.initials: VN
authors.lastname: Cardoso
authors.affiliation: Centro de Desenvolvimento da Tecnologia Nuclear (CDTN), Rua Professor Mário Werneck S/N°, Cidade Universitária, Campus da UFMG, 31120-970, Belo Horizonte, MG, Brasil. Electronic address: antero@cdtn.br.
authors.forename: Antero Silva Ribeiro
authors.initials: AS
authors.lastname: de Andrade
mesh_terms: D000818:Animals; D052157:Aptamers, Nucleotide / Q000737:chemistry / Q000493:pharmacokinetics; D002176:Candida albicans / Q000502:physiology; D002177:Candidiasis / Q000000981:diagnostic imaging; D003545:Cysteine / Q000737:chemistry; D004355:Drug Stability; D007553:Isotope Labeling; D051379:Mice; D011877:Radionuclide Imaging; D013203:Staphylococcal Infections / Q000000981:diagnostic imaging*; D013211:Staphylococcus aureus / Q000502:physiology*; D013667:Technetium; D014018:Tissue Distribution
chemical_list: D052157:Aptamers, Nucleotide; D013667:Technetium; D003545:Cysteine
keywords: (99m)Tc; Aptamers; Diagnosis; Infection; Radiopharmaceutical; Staphylococcus aureus