ORIGINAL ARTICLE   

The Quarterly Journal of Nuclear Medicine and Molecular Imaging 2019 March;63(1):37-47

DOI: 10.23736/S1824-4785.17.02975-2

Copyright © 2017 EDIZIONI MINERVA MEDICA

lingua: Inglese

Comparison of 99mTc-UBI 29-41, 99mTc-ciprofloxacin, 99mTc-ciprofloxacin dithiocarbamate and 111In-biotin for targeting experimental Staphylococcus aureus and Escherichia coli foreign-body infections: an ex-vivo study

Sveva AULETTA ¹, Daniela BALDONI ², Michela VARANI ¹, Filippo GALLI ¹, Iman A. HAJAR ³, Adriano DUATTI ³, Guillermina FERRO-FLORES ⁴, Andrej TRAMPUZ ⁵, Alberto SIGNORE ¹ ✉

¹ Unit of Nuclear Medicine, Department of Medical-Surgical Sciences and of Translational Medicine, Faculty of Medicine and Psychology, Sapienza University, Rome, Italy; ² Infectious Diseases Research Laboratory, Department of Biomedicine, University Hospital, Basel, Switzerland; ³ Laboratory of Nuclear Medicine, Department of Radiological Sciences, University of Ferrara, Ferrara, Italy; ⁴ Department of Radioactive Material, National Institute of Nuclear Investigations, Center of Nuclear Applications on Health, Ocoyoacac, Mexico; ⁵ Unit of Septic Surgery, Center for Musculoskeletal Surgery, Charité, University of Medicine, Berlin, Germany

BACKGROUND: Diagnosis of implant-associated infection is challenging. Several radiopharmaceuticals have been described but direct comparisons are limited. Here we compared in vitro and in an animal model 99mTc-UBI, 99mTc-ciprofloxacin, 99mTcN-CiproCS2 and 111In-DTPA-biotin for targeting E. coli (ATCC 25922) and S. aureus (ATCC 43335).
METHODS: Stability controls were performed with the labelled radiopharmaceuticals during 6 hours in saline and serum. The in vitro binding to viable or killed bacteria was evaluated at 37 °C and 4 °C. For in vivo studies, Teflon cages were subcutaneously implanted in mice, followed by percutaneous infection. Biodistribution of i.v. injected radiolabelled radiopharmaceuticals were evaluated during 24 h in cages and dissected tissues.
RESULTS: Labelling efficiency of all radiopharmaceuticals ranged between 94% and 98%, with high stability both in saline and in human serum. In vitro binding assays displayed a rapid but poor bacterial binding for all tested agents. Similar binding kinetic occurred also with heat-killed and ethanol-killed bacteria. In the tissue cage model, infection was detected at different time points: 99mTc-UBI and 99mTcN-CiproCS2 showed higher infected cage/sterile cage ratio at 24 hours for both E. coli and S. aureus; 99mTc-Ciprofloxacin at 24 hours for both E. coli and at 4 hours for S. aureus; 111In-DTPA-biotin accumulates faster in both E. coli and S. aureus infected cages.
CONCLUSIONS: 99mTc-UBI, 99mTcN-CiproCS2 showed poor in vitro binding but good in vivo binding to E. coli only. 111In-DTPA-biotin showed poor in vitro binding but good in vivo binding to S. aureus and poor to E. coli. 99mTc-Ciprofloxacin showed poor in vitro binding but good in vivo binding to all tested bacteria. The mechanism of accumulation in infected sites remains to be elucidated.

KEY WORDS: Technetium 99m ubiquicidin(29-41) - Technetium Tc 99m ciprofloxacin - 111-indium-ethylenediaminetetracetic acid-biotin - Infection.