Technetium-99m-Labeled Sulfadiazine: a Targeting Radiopharmaceutical for Scintigraphic Imaging of Infectious Foci Due To Escherichia coli in Mouse and Rabbit Models

Abstract

Bacterial infection is one of the vital reasons of morbidity and mortality, especially in developing countries. It appears silently without bothering the geological borders and imposes a grave threat to humanity. Nuclear medicine technique has an important role in helping early diagnosis of deep-seated infections. The aim of this study was to develop a new radiopharmaceutical Tc-labeling sulfadiazine as an infection imaging agent. Radiolabeling of sulfadiazine with technetium-99m (Tc) was carried out using stannous tartrate as a reducing agent in the presence of gentistic acid at pH = 5. The quality control tests revealed ~98% labeling efficiency. Paper chromatographic (PC) and instant thin-layer chromatographic (ITLC) techniques were used to analyze radiochemical yield. Biodistribution and infection specificity of the radiotracer were performed with Escherichia coli (E. coli) infection-induced rats. Scintigraphy and glomerular filtration rate (GFR) study was performed in E. coli-infected rabbits. Scintigraphy indicated E. coli infection targeting potential of Tc-SDZ, while biodistribution study showed minimal uptake ofTc-SDZ in non-targeted tissues. The uptake in the kidneys was found 2.56 ± 0.06, 2.09 ± 0.10, and 1.68 ± 0.09% at 30 min, 1 h, and 4 h, respectively. The infected muscle (target) to non-infected muscle (non-target) ratio (T/NT) was found 4.49 ± 0.04, 6.78 ± 0.07, and 5.59 ± 0.08 at 30 min, 1 h, and 4 h, respectively.

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

“…Both families of antibiotics were extensively studied as radiopharmaceuticals for infection imaging with encouraging and some time discouraging results . However, other electron donor groups such as –S–, –OH, and –NH– groups also involve making coordinate covalent bond with 99m Tc . It is expected two molecules of epirubicin take part in radiochemical reaction with 99m Tc as a bi‐dentate ligand through carbonyl and hydroxyl electron donor oxygen atoms and maximum ions of 99m Tc attains +5 oxidation state.…”

“…Glomerular filtration rate (GFR) study was performed by following the protocol adopted previously . Briefly, a 300 μl aliquot of [ 99m Tc]‐epirubicin was administered into the marginal ear vein of a rabbit in early morning after fasting with drinking water to enhance the urine flow rate.…”

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).…”

“…The majority of the infection models used in the preclinical studies of radiolabeled antibiotics were murine, but some groups used rabbits (10,14,19,20), as the immune system of rabbits is considered to be closer to a human immune system (29). Staphylococcus aureus was used most often to induce infection in experimental animals, but other bacteria such as Mycobaterium tuberculosis (10), Bacteroides fragilis and Dentamoeba fragilis (19), E. coli (20,22), Pseudomonas aeruginosa and Salmonella enterica (21) which are also important from the clinical perspective were utilized as well. Many groups not only imaged the localization of the radiolabeled antibiotics with SPECT or PET but also quantified the images and in some case performed the biodistribution in addition to imaging.…”

99mTc‐labeled antibiotics for infection diagnosis: Mechanism, action, and progress

“…aureus , E . coli , and Bacillus infection‐induced animal model with 3.6 ± 0.22, 6.78 ± 0.07 and 2.21 ± 0.10 T/N.T values, respectively (Ahmed et al, 2017, 2018; Essouissi et al, 2015). The results showed good infection imaging potential.…”