Giulia Anna Follacchio1,2, Alessandro Pala1, Sergio Scaccianoce3, Francesco Monteleone1, Patrick M Colletti4, Domenico Rubello5, Mauro Liberatore1. 1. From the Nuclear Medicine Unit, Department of Radiology, Oncology, and Human Pathology. 2. Departments of Molecular Medicine. 3. Human Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy. 4. Department of Radiology, University of Southern California, Los Angeles, CA. 5. Department of Nuclear Medicine, S. M. della Misericrdia Hospital, Rovigo, Italy.
Abstract
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.
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.