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Antimicrobial Agents and Chemotherapy, May 2004, p. 1624-1629, Vol. 48, No. 5
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.5.1624-1629.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Feasibility of Radioimmunotherapy of Experimental Pneumococcal Infection

E. Dadachova,1* T. Burns,2 R. A. Bryan,1 C. Apostolidis,3 M. W. Brechbiel,4 J. D. Nosanchuk,5 A. Casadevall,2,5 and L. Pirofski2,5

Departments of Nuclear Medicine,1 Microbiology and Immunology,2 Medicine, Albert Einstein College of Medicine, Bronx, New York,5 Institute for Transuranium Elements, Heidelberg, Germany,3 National Cancer Institute, National Institutes of Health, Bethesda, Maryland4

Received 1 October 2003/ Returned for modification 29 November 2003/ Accepted 21 January 2004

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 213Bi as the radionuclide for conjugation to the antibody. Incubation of serotype 8 S. pneumoniae with 213Bi-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 213Bi-D11-treated group (80 µCi) 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.

* Corresponding author. Mailing address: Department of Nuclear Medicine, Albert Einstein College of Medicine, 1695A Eastchester Rd., Bronx, NY 10461. Phone: (718) 405-8485. Fax: (718) 405-8457. E-mail: edadacho{at}aecom.yu.edu.

Antimicrobial Agents and Chemotherapy, May 2004, p. 1624-1629, Vol. 48, No. 5
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.5.1624-1629.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Dadachova, E., Bryan, R. A., Huang, X., Ortiz, G., Moadel, T., Casadevall, A. (2007). Comparative Evaluation of Capsular Polysaccharide-Specific IgM and IgG Antibodies and F(ab')2 and Fab Fragments as Delivery Vehicles for Radioimmunotherapy of Fungal Infection. Clin. Cancer Res. 13: 5629s-5635s [Abstract] [Full Text]  
  • Martinez, L. R., Bryan, R. A., Apostolidis, C., Morgenstern, A., Casadevall, A., Dadachova, E. (2006). Antibody-guided alpha radiation effectively damages fungal biofilms.. Antimicrob. Agents Chemother. 50: 2132-2136 [Abstract] [Full Text]  
  • Bryan, R. A., Zaragoza, O., Zhang, T., Ortiz, G., Casadevall, A., Dadachova, E. (2005). Radiological Studies Reveal Radial Differences in the Architecture of the Polysaccharide Capsule of Cryptococcus neoformans. Eukaryot Cell 4: 465-475 [Abstract] [Full Text]  


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