title: Feasibility of radioimmunotherapy of experimental pneumococcal infection.
abstract: Streptococcus pneumoniae is an important cause of community-acquired pneumonia, meningitis, and bacteremia. The problem of pneumococcal disease is exacerbated by increasing drug resistance. Furthermore, patients with impaired immunity are at high risk for invasive pneumococcal infections. Thus, there is an urgent need for new approaches to antimicrobial therapy. Antibody therapies take advantage of the specificity and high affinity of the antigen-antibody interaction to deliver antibacterial compounds to a site of infection in the form of naked or conjugated antibodies. We have recently established that radioimmunotherapy (RIT) can be used to treat experimental fungal infections in mice. In the present study, we investigated the feasibility of applying a RIT approach to the treatment of S. pneumoniae infection by evaluating the susceptibility of S. pneumoniae to radiolabeled antibody in vitro and in an animal infection model. For the specific antibody carrier, we used human monoclonal antibody D11, which binds to pneumococcal capsular polysaccharide 8. We have selected the alpha particle emitter (213)Bi as the radionuclide for conjugation to the antibody. Incubation of serotype 8 S. pneumoniae with (213)Bi-D11 resulted in dose-dependent killing of bacteria. RIT of S. pneumoniae infection in C57BL/6 mice showed that 60% more mice survived in the (213)Bi-D11-treated group (80 micro Ci) than in the untreated group (P < 0.01). The treatment did not cause hematological toxicity, as demonstrated by platelet counts. This feasibility study establishes that RIT can be applied to the treatment of bacterial infections.
authors.affiliation: Department of Nuclear Medicine, Albert Einstein College of Medicine, Bronx, New York 10461, USA. edadacho@aecom.yu.edu
authors.forename: E
authors.initials: E
authors.lastname: Dadachova
authors.forename: T
authors.initials: T
authors.lastname: Burns
authors.forename: R A
authors.initials: RA
authors.lastname: Bryan
authors.forename: C
authors.initials: C
authors.lastname: Apostolidis
authors.forename: M W
authors.initials: MW
authors.lastname: Brechbiel
authors.forename: J D
authors.initials: JD
authors.lastname: Nosanchuk
authors.forename: A
authors.initials: A
authors.lastname: Casadevall
authors.forename: L
authors.initials: L
authors.lastname: Pirofski
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use; D001729:Bismuth; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D010976:Platelet Count; D011008:Pneumococcal Infections / Q000382:microbiology / Q000628:therapy*; D016499:Radioimmunotherapy / Q000009:adverse effects; D011868:Radioisotopes; D013296:Streptococcus pneumoniae / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D011868:Radioisotopes; D001729:Bismuth