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In Vivo Microbial Targeting of 99mTc-Labeled Human β-Defensin-3 in a Rat Model of Infection
Giulia Anna Follacchio1,2, Alessandro Pala1, Sergio Scaccianoce3
1From the Nuclear Medicine Unit, Department of Radiology, Oncology, and Human Pathology.
Objective:
Differentiation of infection from aseptic inflammation represents a major clinical issue. None of the commercially available compounds (labeled granulocytes, antigranulocyte antibodies, Ga-citrate, labeled immunoglobulin G, F-FDG) is capable of this differentiation, producing a nonnegligible false-positive rate. Recently, our group reported on a reliable labeling procedure of the antimicrobial peptide human β-defensin 3 (HBD-3) with Tc. The aim of this study was to evaluate in vivo Tc-HBD-3 uptake in a rat model of infection.
Methods:
Recombinant HBD-3 was radiolabeled with Tc. Radiolabeling yield and specific activity of the compound were calculated. Chromatographic behavior and biological activity of Tc-HBD-3 were also assessed. An experimental model involving Staphylococcus aureus-induced infection and carrageenan-induced aseptic inflammation was performed in 5 Wistar rats. Serial planar scintigraphic acquisitions were performed from 15 to 180 minutes after Tc-HBD-3 intravenous administration. Radiotracer uptake was evaluated qualitatively and semiquantitatively as a target-to-nontarget ratio.
Results:
Radiolabeling yield of Tc-HBD-3 was 70% with a specific activity of 6 to 8 MBq/μg. A significant and progressive Tc-HBD-3 uptake was observed in the site of S. aureus-induced infection, with a maximum average target-to-nontarget ratio of 5.7-fold higher in the infection site compared with an inflammation site observed at 140 minutes.
Conclusions:
In vivo imaging with Tc-HBD-3 in a rat model of S. aureus-induced infection demonstrated favorable uptake in the infection site compared with sterile inflammation and background. These promising results, together with previous ex vivo uptake and toxicity assessment, suggest the potential of Tc-HBD-3 as a novel agent for specific infection imaging.
Insights
Technetium-labeled human beta-defensin 3 (Tc-HBD-3) shows promising uptake in infection sites. This novel radiotracer may help differentiate infection from sterile inflammation in vivo.
Area of Science:
- Nuclear medicine
- Infectious disease imaging
- Radiopharmaceutical development
Background:
- Differentiating infection from aseptic inflammation is clinically challenging.
- Current imaging agents have limitations, including false-positive rates.
- Antimicrobial peptides like human beta-defensin 3 (HBD-3) show potential for targeted imaging.
Purpose of the Study:
- To evaluate the in vivo uptake of Tc-HBD-3 in a rat model.
- To assess Tc-HBD-3's ability to distinguish infection from sterile inflammation.
Main Methods:
- Recombinant HBD-3 was radiolabeled with Technetium-99m (Tc).
- Tc-HBD-3's radiolabeling yield, specific activity, and biological activity were assessed.
- Infection and aseptic inflammation models were established in rats.
- Serial scintigraphic imaging was performed after Tc-HBD-3 administration.
Main Results:
- Tc-HBD-3 demonstrated a radiolabeling yield of 70% and specific activity of 6-8 MBq/μg.
- Significant and progressive Tc-HBD-3 uptake was observed at the site of Staphylococcus aureus infection.
- The target-to-nontarget ratio in the infection site was 5.7-fold higher than in the inflammation site at 140 minutes.
Conclusions:
- Tc-HBD-3 imaging in a rat model showed preferential uptake at infection sites.
- These findings suggest Tc-HBD-3's potential as a novel agent for specific infection imaging.
- Further studies are warranted to validate Tc-HBD-3 for clinical use in differentiating infection from inflammation.
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