Abstract
The accurate and early diagnosis of infection is an important feature in the biomedical sciences for better treatment and to decrease the rate of morbidity associated with diseases. Doxycycline (DC) is a semisynthetic antibiotic that belongs to tetracycline family and usually prescribed to treat a variety of infections. The objective of the present research work was to develop a new radiopharmaceutical 99mTc-Doxycycline (99mTc-DC), by using SnCl2·2H2O as a reducing agent for diagnostic applications. It was confirmed through this study that 99mTc-DC possessed high radiolabeling yield (95%). In vitro studies were performed by incubating 99mTc-DC in human serum at 37 °C. The in vitro binding interaction of the labeled antibiotic was analyzed with bacterial strain (live Staphylococcus aureus cells), and its stability was further determined. Moreover, for in vivo infection imaging study, the infection was induced with S. aureus (gram positive) cells intramuscularly injected in mice models followed by biodistribution studies for 99mTc-DC that were performed. Biodistribution studies of 99mTc-DC showed that the radiotracer was significantly accumulated at the site of infection and indicated the renal route of excretion. Scintigraphic images obtained as a result of in vivo study showed good uptake of prepared radiotracer (99mTc-DC) in the infectious lesions at 1-, 4-, and 24-h post-injection. Target-to-non-target ratios for 99mTc-DC were significantly different for the infectious lesions and non-infected tissues and remained 2.13 ± 0.3 up to 24-h post-injection of 99mTc-DC. 99mTc-DC showed preferential binding to living bacterial infected sites as compared to other parts of the body, and thus it can be inferred that 99mTc-DC might be a potential candidate to diagnose the infection.
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Syed Faheem Askari Rizvi: Conceptualization, methodology, validation, investigation, and writing—original draft. Tania Jabbar: Resources and methodology. Wajeehah Shahid: Resources and project administration. Mahmoud Hamdi Sanad: Formal analysis and visualization. Haixia Zhang: Validation, resources, writing (review and editing), and supervision.
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All applicable national, international, and institutional guidelines for the care and use of animals were followed. Animal studies were approved by the Institutional Ethical Review Committee for Care and Use of Animals (IERCCUA), Institute of Microbiology and Biochemistry (IMBB), The University of Lahore (UOL), Lahore, Pakistan, and performed in compliance with guidelines from the National Institute of Health, Islamabad, Pakistan. This article does not contain any human studies performed by any of the authors.
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Rizvi, S.F.A., Jabbar, T., Shahid, W. et al. Facile One-Pot Strategy for Radiosynthesis of 99mTc-Doxycycline to Diagnose Staphylococcus aureus in Infectious Animal Models. Appl Biochem Biotechnol 194, 2672–2683 (2022). https://doi.org/10.1007/s12010-022-03856-1
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DOI: https://doi.org/10.1007/s12010-022-03856-1