Facile One-Pot Strategy for Radiosynthesis of 99mTc-Doxycycline to Diagnose Staphylococcus aureus in Infectious Animal Models
2022
Rizvi, Syed Faheem Askari | Jabbar, Tania | Shahid, Wajeehah | Sanad, M. H. | Zhang, Haixia
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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