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In Vivo Microbial Targeting of 99mTc-Labeled Human β-Defensin-3 in a Rat Model of Infection

Follacchio, Giulia Anna MD*,†; Pala, Alessandro MD*; Scaccianoce, Sergio MD; Monteleone, Francesco MD*; Colletti, Patrick M. MD§; Rubello, Domenico MD; Liberatore, Mauro MD*

doi: 10.1097/RLU.0000000000002713
Original Articles
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Objective Differentiation of infection from aseptic inflammation represents a major clinical issue. None of the commercially available compounds (labeled granulocytes, antigranulocyte antibodies, 67Ga-citrate, labeled immunoglobulin G, 18F-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 99mTc. The aim of this study was to evaluate in vivo 99mTc-HBD-3 uptake in a rat model of infection.

Methods Recombinant HBD-3 was radiolabeled with 99mTc. Radiolabeling yield and specific activity of the compound were calculated. Chromatographic behavior and biological activity of 99mTc-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 99mTc-HBD-3 intravenous administration. Radiotracer uptake was evaluated qualitatively and semiquantitatively as a target-to-nontarget ratio.

Results Radiolabeling yield of 99mTc-HBD-3 was 70% with a specific activity of 6 to 8 MBq/μg. A significant and progressive 99mTc-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 99mTc-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 99mTc-HBD-3 as a novel agent for specific infection imaging.

From the *Nuclear Medicine Unit, Department of Radiology, Oncology, and Human Pathology

Departments of Molecular Medicine

Human Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy

§Department of Radiology, University of Southern California, Los Angeles, CA

Department of Nuclear Medicine, S. M. della Misericrdia Hospital, Rovigo, Italy.

Received for publication May 17, 2019; revision accepted May 31, 2019.

Conflicts of interest and sources of funding: none declared.

Correspondence to: Giulia Anna Follacchio, MD, Nuclear Medicine Unit, Department of Radiology, Oncology and Human Pathology, AOU Policlinico “Umberto I,” Sapienza University of Rome, 324, Viale Regina Elena, 00161, Rome, Italy. E-mail: giuliaanna.follacchio@uniroma1.it.

Online date: July 15, 2019

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