Radiosynthesis and Preclinical Evaluation of [[sup.99m]Tc]Tc-Tigecycline Radiopharmaceutical to Diagnose Bacterial Infections

• Published in: Pharmaceuticals (Basel, Switzerland) Vol. 17; no. 10
• Main Authors: Saleem, Syeda Marab, Jabbar, Tania, Imran, Muhammad Babar, Noureen, Asma, Sherazi, Tauqir A, Afzal, Muhammad Shahzad, Rab Nawaz, Hafiza Zahra, Ramadan, Mohamed Fawzy, Alkahtani, Abdullah M, Alsuwat, Meshari A, Almubarak, Hassan Ali, Momenah, Maha Abdullah, Naqvi, Syed Ali Raza
• Format: Journal Article
• Language: English
• Published: MDPI AG 01-10-2024
• Subjects: Bacterial infections; Diagnosis; Diagnostic imaging; Isotopes; Methods; Technetium; Pakistan
• ISSN: 1424-8247; 1424-8247
• DOI: 10.3390/ph17101283

Background/Objectives: As a primary source of mortality and disability, bacterial infections continue to develop a severe threat to humanity. Nuclear medicine imaging (NMI) is known for its promising potential to diagnose deep-seated bacterial infections. This work aims to develop a new technetium-99m ([sup.99m] Tc) labeled tigecycline radiopharmaceutical as an infection imaging agent. Methods: Reduced [sup.99m] Tc was used to make a coordinate complex with tigecycline at pH 7.7–7.9 at room temperature. Instantaneous thin-layer chromatography impregnated with silica gel (ITLC-SG) and ray detector equipped high-performance liquid chromatography (ray-HPLC) was performed to access the radiolabeling yield and radiochemical purity (RCP). Results: More than 91% labeling efficiency was achieved after 25 min of mild shaking of the reaction mixture. The radiolabeled complex was found intact up to 4 h in saline. Staphylococcus aureus (S. aureus ) and Escherichia coli (E. coli ) infection-induced rats were used to record the biodistribution of the radiopharmaceutical and its target specificity; 2 h’ post-injection biodistribution revealed a 2.39 ± 0.29 target/non-target (T/NT) ratio in the E. coli infection-induced animal model, while a 2.9 ± 0.31 T/NT value was recorded in the S. aureus bacterial infection-induced animal model. [[sup.99m] Tc]Tc-tigecycline scintigraphy was performed in healthy rabbits using a single photon emission computed tomography (SPECT) camera. Scintigrams showed normal kidney perfusion and excretion into the bladder. Conclusion: In conclusion, the newly developed [[sup.99m] Tc]Tc-tigecycline radiopharmaceutical could be considered to diagnose broad-spectrum bacterial infections.