Toxicity assessment of (99m)technetium-labeled human beta-defensin-3 in CD1 mice

Objective: Human beta-defensin-3 (HBD-3) is an antimicrobial peptide which is up-regulated during 99m inflammation. Based on the previously demonstrated capacity of technetium-99m ( Tc) labelled HBD-3 of distinguishing infection from inflammation in rats, we have decided to collect information on the potential toxicity of the tracer in view of its possible use for imaging in humans. Materials and Methods: 99m Recombinant HBD-3 underwent labeling with Tc. The CD1 mice were selected as standard rodent species. Ten mice, 5 male and 5 female, were subjected to physical examination and housed in a dedicated room in 5 per cage. After 9 days pre-test period, all mice were weighted for dose adjustment and received 99m intravenously 6mcg/mouse of Tc-HBD-3. Mortality was recorded daily, while body weight was registered once a week. Clinical observation of animals was performed daily for sickness symptoms due to 99m the drug treatment. At day 19 a second dose of 6mcg/mouse Tc-HBD-3, was administered. Twenty-four hours after the second dose (day 20) the animals were euthanized. A piece of liver, kidneys, heart and lungs was collected for histopathological analysis. Results:Our results showed that the labelled-HBD-3 dose did not induce significant toxicity in mice. Of course these parameters were not sufficient to authorize use in humans. This non-toxic dose of HBD-3 when translated from animals to humans resulted in an equivalent dose of approximately 25 times higher than that needed for imaging. Conclusion:Our non toxicity data of 99m using Tc-beta-defensin-3 in mice offer a further indication in favour of the clinical use of this radiopharmaceutical in all cases where discrimination between infection and inflammation is needed.