Safety Evaluation of an Alpha-Emitter Bismuth-213 Labeled Antibody to (1→3)-β-Glucan in Healthy Dogs as a Prelude for a Trial in Companion Dogs with Invasive Fungal Infections.

Background: With the limited options available for therapy to treat invasive fungal infections (IFI), radioimmunotherapy (RIT) can potentially offer an effective alternative treatment. Microorganism-specific monoclonal antibodies have shown promising results in the experimental treatment of fungal, bacterial, and viral infections, including our recent and encouraging results from treating mice infected withBlastomyces dermatitidiswith(213)Bi-labeled antibody 400-2 to (1 -> 3)-beta-glucan. In this work, we performed a safety study of(213)Bi-400-2 antibody in healthy dogs as a prelude for a clinical trial in companion dogs with acquired invasive fungal infections and later on in human patients with IFI.Methods: Three female beagle dogs (approximate to 6.1 kg body weight) were treated intravenously with 155.3, 142.5, or 133.2 MBq of(213)Bi-400-2 given as three subfractions over an 8 h period. RBC, WBC, platelet, and blood serum biochemistry parameters were measured periodically for 6 months post injection.Results: No significant acute or long-term side effects were observed after RIT injections; only a few parameters were mildly and transiently outside reference change value limits, and a transient atypical morphology was observed in the circulating lymphocyte population of two dogs.Conclusions: These results demonstrate the safety of systemic(213)Bi-400-2 administration in dogs and provide encouragement to pursue evaluation of RIT of IFI in companion dogs.