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Article

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

1
College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada
2
Western College of Veterinary Medicine, Saskatoon, SK S7N 5B4, Canada
3
Safety Resources, University of Saskatchewan, Saskatoon, SK S7N 5C5, Canada
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
These authors shared senior authorship.
Academic Editors: Alessandra Boschi and Petra Martini
Molecules 2020, 25(16), 3604; https://doi.org/10.3390/molecules25163604
Received: 3 July 2020 / Revised: 4 August 2020 / Accepted: 6 August 2020 / Published: 8 August 2020
(This article belongs to the Special Issue Metal-Based Radiopharmaceuticals in Inorganic Chemistry)
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 with Blastomyces dermatitidis with 213Bi-labeled antibody 400-2 to (1→3)-β-glucan. In this work, we performed a safety study of 213Bi-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 (≈6.1 kg body weight) were treated intravenously with 155.3, 142.5, or 133.2 MBq of 213Bi-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 213Bi-400-2 administration in dogs and provide encouragement to pursue evaluation of RIT of IFI in companion dogs. View Full-Text
Keywords: radioimmunotherapy; bismuth-213; invasive fungal infections; 1-3-beta-glucan; dogs radioimmunotherapy; bismuth-213; invasive fungal infections; 1-3-beta-glucan; dogs
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MDPI and ACS Style

Helal, M.; Allen, K.J.H.; Burgess, H.; Jiao, R.; Malo, M.E.; Hutcheson, M.; Dadachova, E.; Snead, E. 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. Molecules 2020, 25, 3604. https://doi.org/10.3390/molecules25163604

AMA Style

Helal M, Allen KJH, Burgess H, Jiao R, Malo ME, Hutcheson M, Dadachova E, Snead E. 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. Molecules. 2020; 25(16):3604. https://doi.org/10.3390/molecules25163604

Chicago/Turabian Style

Helal, Muath, Kevin J.H. Allen, Hilary Burgess, Rubin Jiao, Mackenzie E. Malo, Matthew Hutcheson, Ekaterina Dadachova, and Elisabeth Snead. 2020. "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" Molecules 25, no. 16: 3604. https://doi.org/10.3390/molecules25163604

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