^99mTc‐Ceftizoxime: Synthesis, characterization and its use in diagnosis of diabetic foot osteomyelitis

Abstract

Introduction: The diagnosis of diabetic foot osteomyelitis is crucial and challenging for the proper management of diabetic foot. 99m Tc labelled Ceftizoxime was used as a non-invasive diagnostic agent for diabetic foot osteomyelitis. Methods: Ceftizoxime [CFT], a third generation cephalosporin, was used in a simple and direct method for the synthesis of 99m TcO 4 À labelled infection imaging agent with stannous chloride as reducing agent. Its radiochemical purity was checked by thin Layer chromatography. Partition co-efficient was measured with phosphate buffer and chloroform. The radiochemical complex was injected to control and infected animal model for 3 hours in-vivo localization studied with the help of dual head gamma camera. The labelled complexes were injected to 5 patients of known type II diabetes mellitus suspected of diabetic foot osteomyelitis. All patients underwent dynamic and static 99m Tc-MDP and 99m Tc-CFT scans.Results: The synthesized radio labelled complex was 98.8% pure, with hydrophilic character. When injected to animal model, at 120 minutes, 49.3% was localized in foci of infection with 3.35% in liver and excretion through kidney. Human studies were interpreted as true or false positive and true or false negative based on bone histopathology/culture and clinical follow-up. We found that of 5 patients, 2 were true positive, 2 as true negative with no false positive or negative and 01 patient had soft tissue infection.Conclusion: This study showed that 99m Tc-CFT labelled complex could be used for detection of diabetic foot osteomyelitis; however, further confirmation of results with a larger patient population would be optimal.Key words: 99m Tc labelled antibiotic; bone infection imaging agent; non-invasive imaging agent; 99m Tc-Ceftizoxime as bone osteomyelitis imaging agent.

Diagnostic Accuracy of 99 MTC Labelled Ubiquicidin (29-41) Spect/Ct for Diagnosis of Osteomyelitis in Diabetic Foot

“…Labeled leucocytes have been extensively studied with 72-100% reported sensitivity and 67-100% reported specificities [13][14] . This technique is laborious, time consuming and technically demanding.…”

“…Out of all labeled antibiotics, only Tc-99m Ciprofloxacin (Infecton) was investigated for identification of diabetic foot infection and established less precise than labeled leukocyte imaging for diabetic foot osteomyelitis 14 . Ceftizoxime was labeled with Tc-99m and employed in diabetic foot infection, results demonstrated excellent sensitivity and specificity 15 .…”

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

“…Other published study on 99m Tc‐ceftizoxime scintigraphy using four groups of patients having different implants such as titanium implants (group A; n = 5) contaminated titanium implants (group B; n = 5) and sterile stainless steel implants (group C; n = 5) and contaminated stainless steel implants (group D; n = 5) showed 0.98 ± 0.04, 1.68 ± 0.62, 1.22 ± 0.08, and 2.14 ± 0.84 infection to normal muscle ratio, respectively (Teixeira et al, 2018). A study was also reported which indicated the potential of 99m Tc‐ceftizoxime to diagnose diabetic foot osteomyelitis infection (Ahmed et al, 2019). The summary of results of all the cephalosporins labeled with 99m Tc and their potential as infection imaging against common infection causing bacterial strains is shown in Table 1 (Section cephalosporin).…”

“…99m Tc‐ceftizoxime was first developed and studied using in vitro model of E . coli which showed 83% inhibition activity as compared to unlabeled ceftizoxime (Ahmed et al, 2019). The results of this study led to the development of 99m Tc‐ceftizoxime kit formulation with 92% labeling efficiency.…”

Molecular Imaging of Diabetic Foot Infections: New Tools for Old Questions

“…More recently, the PET agent 68 Ga-NOTA-UBI was used for imaging DFI in a small patient sample [67]. Similar studies have evaluated 99m Tc-radiolabeled antibiotics, which suggest they could be used for the detection of osteomyelitis [68]. However, some radiolabeled antibiotics and antimicrobial peptides have been shown to have poor specificity [69,70].…”