Radiosynthesis and Preclinical Evaluation of [^99mTc]Tc-Tigecycline Radiopharmaceutical to Diagnose Bacterial Infections

• Main Authors: Syeda Marab Saleem (Author), Tania Jabbar (Author), Muhammad Babar Imran (Author), Asma Noureen (Author), Tauqir A. Sherazi (Author), Muhammad Shahzad Afzal (Author), Hafiza Zahra Rab Nawaz (Author), Mohamed Fawzy Ramadan (Author), Abdullah M. Alkahtani (Author), Meshari A. Alsuwat (Author), Hassan Ali Almubarak (Author), Maha Abdullah Momenah (Author), Syed Ali Raza Naqvi (Author)
• Format: Book
• Published: MDPI AG, 2024-09-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.3390/ph17101283; 1424-8247
• Keywords: antibiotics; tigecycline; radioisotope; nuclear medicine; radiopharmaceuticals; infection; Medicine; R; Pharmacy and materia medica; RS1-441
• Source: Pharmaceuticals, Vol 17, Iss 10, p 1283 (2024)

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 (^99mTc) labeled tigecycline radiopharmaceutical as an infection imaging agent. Methods: Reduced ^99mTc 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. <i>Staphylococcus aureus</i> (<i>S. aureus</i>) and <i>Escherichia coli</i> (<i>E. coli</i>) 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 <i>E. coli</i> infection-induced animal model, while a 2.9 ± 0.31 T/NT value was recorded in the <i>S. aureus</i> bacterial infection-induced animal model. [^99mTc]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 [^99mTc]Tc-tigecycline radiopharmaceutical could be considered to diagnose broad-spectrum bacterial infections.