Radiolabeled Organism-Specific Antibodies for Diagnosis and Therapy of Infections

Abstract

There is enormous need for new approaches to diagnosis and therapy of infectious diseases due to increasing number of immunosuppressed individuals in whom antimicrobial therapies are not effective; growing prevalence of diseases caused by highly resistant microorganisms, some of which are not susceptible to any currently available antimicrobial agents; and a dearth of new anti-microbial drugs in the development pipeline. To further complicate matters new microbes are regularly identified and for many there are no available therapies and there is the specter of biological weapons. Organism-specific radiolabeled antibodies have been used both in pre-clinical and clinical settings for diagnosis of infection, however, their potential has never been fully realized. Radioimmunotherapy (RIT), a therapeutic modality originally developed for cancer treatment, has been recently suggested as a novel therapy for treatment of variety of infectious diseases. The feasibility of using RIT for infections was demonstrated by treating murine cryptococcosis with a monoclonal antibody to Cryptococcus neoformans capsular glucuronoxylomannan labeled with Bismuth-213 or Rhenium-188. Those finding were subsequently extended to treatment of experimental bacterial (Streptococcus pneumonia) and viral (HIV-1) infections. Treatment did not cause acute hematologic toxicity in treated animals. We believed that diagnosis and treatment of infection with radiolabeled antibodies holds enormous potential as the technology for this is largely in place and that the only requirements are availability of microbe-specific monoclonal antibodies and suitable radionuclides. We anticipate that targeting microbes for both diagnosis and therapy will be easier than targeting neoplastic cells when the enormous antigenic differences between host and microbes are taken into consideration. However, considerable basic work is still required for finding the optimal conditions for clinical use of radiolabeled organism specific antibodies.