Preparation, molecular docking, and biological evaluation of radioiodinated cefaclor for inflammation detection

Inflammation serves as a natural defense mechanism; however, its persistence can lead to chronic diseases with serious clinical consequences. Early detection of inflammation is therefore critical to slowing disease progression and improving therapeutic outcomes. In this study, cefaclor (Cefa) was successfully radiolabeled with iodine-131 via electrophilic substitution to facilitate the detection of infected and inflamed muscles in mouse models. The labeling reaction was carried out with 100 µg of Cefa and 100 µg of iodogen, using glass frits as the oxidizing system at pH 7 and 60 °C, with 10 µL of Na131I for 20 min. The resulting [131I]Cefa was purified by high-performance liquid chromatography (HPLC). Molecular modeling was performed in the Molecular Operating Environment (MOE) to evaluate the compound’s structure and binding affinity. The labeling process was optimized to achieve a radiolabeling efficiency of 90 ± 0.56%, and stability of about 89 ± 0.5% at 4 h. Docking simulations confirmed strong binding of [131I]Cefa to bacterial DNA gyrase B, supporting its potential as a targeted imaging agent. Biological evaluation in mouse models demonstrated notable tracer accumulation in both septic and sterile inflammatory sites. Uptake values reached 28 ± 1.5%ID/organ in infected muscles and 16 ± 1.5%ID/organ in sterile inflammation at 120 minutes post-injection. The target-to-non-target (T/NT) ratios were 5.28 for infected muscles and 2.1 for sterile inflammation, indicating effective differentiation between bacterial (septic) and non-bacterial (aseptic) inflammatory foci. The radiolabeled [131I]Cefa compound exhibits promising diagnostic capabilities for distinguishing bacterial infections from sterile inflammation. Its high radiolabeling efficiency, strong molecular binding, and selective in vivo uptake support its potential utility as a non-invasive imaging agent for early detection and characterization of inflammatory conditions. Objective: To develop a radiolabeled cefaclor compound ([131 I] Cefa) for early imaging and differentiation between bacterial infections and sterile inflammation. Radiolabeling Method: Cefaclor was labeled with iodine-131 via electrophilic substitution, achieving a high radiochemical yield of 90 ± 0.56% using iodogen and glass frits as the oxidizing system. Structural Analysis: Molecular modeling and docking simulations confirmed strong binding of [131 I] Cefa to bacterial DNA gyrase B, supporting its role as a targeted imaging agent. In Vivo Findings: In mouse models, the compound showed significant uptake in infected (28± 1.5%) and sterile inflamed tissues (16 ± 1.5%) at 120 minutes post-injection. Diagnostic Value: The target-to-non-target ratios (28 for infection, 2.1 for sterile inflammation) demonstrate the compound’s potential to distinguish between infectious and non-infectious inflammation.