^99m Tc-tazobactam, a novel infection imaging agent: Radiosynthesis, quality control, biodistribution, and infection imaging studies

Abstract

The radiolabeled drug Tc-tazobactam ( Tc-TZB) was developed and assessed as an infection imaging agent in Pseudomonas aeruginosa and Salmonella enterica infection-induced animal models by comparing with inflammation induced animal models. Radiosynthesis of Tc-TZB was assessed while changing ligand concentration, reducing agent concentration, pH, and reaction time while keeping radioactivity constant (~370 MBq). Percent labeling of the resulting complex was measured using paper chromatography and instant thin layer chromatography. The analysis of the Tc-TZB complex indicated >95% labeling yield and electrophoresis revealed complex is neutral in nature. The biodistribution study also showed predominantly renal excretion; however liver, stomach, and intestine also showed slight tracer agent uptake. The agent significantly accumulated in Pseudomonas aeruginosa and Salmonella enterica infection induced tissues 3.58 ± 0.26% and 2.43 ± 0.42% respectively at 1 hour postinjection. The inflamed tissue failed to uptake noticeable activity at 1 hour time point. The scintigraphic study results were found in accordance with biodistribution pattern. On the basis of our preliminary results, the newly developed Tc-TZB can be used to diagnose bacterial infection and to discriminate between infected and inflamed tissues.

Technetium‐99m radiolabeling and biological study of epirubicin for in vivo imaging of multi‐drug‐resistant Staphylococcus aureus infections via single photon emission computed tomography

“…A dual‐head ARGUS EPIC (ADAC) SPECT gamma camera system connected with online dedicated system was used for the scintigraphy study, following the protocol described by Naqvi et al . Briefly, 36 hr prior to SPECT scintigraphy study, the infection was induced into right thigh muscles of rabbit by injecting clinically isolated multi‐drug resistant S. aureus bacterial strain (ST339).…”

Highlights of the Latest Developments in Radiopharmaceuticals for Infection Imaging and Future Perspectives

“…Imaging of bacterial infections is by far the most developed area of infection imaging. Multiple antibiotics with a variety of mechanisms of action such as ciproflaxicin (7,8) and nitrofuryl thiosemicarbazone (7), fluoroquinolone (9), isoniazid (10), ofloxacin (11,12), cephalosporin (13), clindamycin (14), doxycycline (15), ceftizoxime (16,17), cefotaxime (18), tinidazole (19), sulfadiazine (20), tazobactam (21) and metronidazole (22) were radiolabeled with 99m Tc to enable SPECT imaging in the pre-clinical models of infection. The majority of the authors employed Sn(+2) salts as the reducing agents for 99m Tc which produced [ 99m Tc-O](3+) core, while in several publications 99m Tc carbonyl or [ 99m Tc-N](2+) cores were utilized (7,8,11).…”

99mTc-radiolabeled Levofloxacin and micelles as infection and inflammation imaging agents

“…For the purpose of obtaining efficient and maximum radiolabeling, optimum amount of Levofloxacin, reducing agent, pH and incubation time were evaluated. The highest radiolabeling yield was calculated after passing 99m Tc-Levofloxacin through a 0.22 μm filter and by ITLC analysis [36,42,44,55].…”

“…Other fluoroquinolone family antibiotics were also labeled for this purpose [26]. By the improvements in the production of alternative severe acute respiratory syndrome (SARS) antibiotics and growing drug resistance, a variety of 99m Tc-labeled flouroquinolone and cephalosporin antibiotics were prepared including 99m Tc-Pefloxacin [27], 99m Tc-Lomefloxacin and 99m Tc-Ofloxacin [28], 99m Tc-Sparafloxacin [29], 99m Tc-Difloxacin [30], 99m Tc-Moxifloxacin [31], 99m Tc-Gemifloxacin [32], 99m Tc-Rufloxacin [33], 99m Tc-Clinafloxacin [34], 99m Tc-Sitafloxacin [35], 99m Tc-Levofloxacin [36], 99m Tc-Temafloxacin [37], 99m Tc-Ceftizoxime [38], 99m Tc-Cefuroxime [5], 99m Tc-Ceftriaxone [39], 99m Tc-Cefotaxime [40] and 99m Tc-Cefoperazone [41,42]. Radiolabeled antibiotics have been used for the diagnosis of infection.…”