Synthesis of 99mTc‐roxithromycin: A novel diagnostic agent to discriminate between septic and aseptic inflammation. (29th October 2018)

• Record Type: Journal Article
• Authors: Rizvi, Syed Faheem Askari; Tariq, Saleha; Mehdi, Muhammad; Hassan, Ahmad Junaid
• Is Part Of: Chemical biology & drug design. Volume 93:Number 6(2019)
• Page Start: 1166
• Page End: 1174
• Publication Date: 2018-10-29
• Subjects: 99mTc‐roxithromycin -- erythromycin -- macrolide antibiotics -- radio‐HPLC -- S. aureus -- turpentine oil; Drugs -- Design -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; 615.19005
• DOI: 10.1111/cbdd.13412
• Languages: English
• ISSNs: 1747-0277

Abstract

Abstract: Roxithromycin is a second‐generation macrolide antibiotic derived from erythromycin. In the current study, roxithromycin (ROX) was successfully labeled with technetium‐99m for early diagnosis of bacterial infection and discrimination between septic and aseptic inflammation. The highest radiochemical purity of ≥95% was achieved by investigating different labeling parameters such as pH, ligand/reducing agent concentration, temperature, and amount of stabilizing agent. For this purpose, 0.3–0.5 mg ligand, 2–6 μg SnCl2 ·2H2 O as a reducing agent at basic pH (8–10 pH) and 2 mg mannitol used as a stabilizing agent, in the end, 370 MBq 99m Tc added into the reaction vials and incubated for a wide range of temperature (−4 to 65°C). The percent radiochemical purity of 99m Tc‐roxithromycin was assessed with the help of the radio‐thin‐layer chromatography technique. The characterization studies were carried out using electrophoresis and Radio‐HPLC techniques as well as saline stability and serum stability studies were also performed. Furthermore, biodistribution study was also performed in an inflamed animal model to discriminate between septic (heat‐killed Staphylococcus aureus ) and aseptic (turpentine oil) inflammatory lesions. The results were elaborated that 99m Tc‐roxithromycin ( 99m Tc‐ROX) was clearly bounded at the septic inflammation site (T/NT ratio of 7.08 ± 1.14) at 30 min postadministration, and maximum accumulation was seen in heart, lungs, liver, stomach, kidneys, and intestine. The results were suggested that 99m Tc‐ROX might be used to discriminate between septic and aseptic inflammatory lesions at an early stage. Abstract : Roxithromycin (second‐generation macrolide antibiotic) was labeled with gamma‐emitting radionuclide (i.e., 99m Tc) to diagnose the early stage bacterial action by accumulation of the radiopharmaceutical at targeted site (infected by Staphylococcus aureus ). In vivo studies of newly synthesized radiopharmaceutical illustrated that 99m Tc‐roxithromycin can be used as potential infection imaging agent.