Synthesis of 99m Tc-roxithromycin: A novel diagnostic agent to discriminate between septic and aseptic inflammation.

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.

Synthesis and preclinical evaluation of bactericidal agent isolated from soil bacterium (Streptomyces): a novel diagnostic technique to enhance anticancer efficacy through radiosynthesis.

OBJECTIVES: Dactinomycin is a well-known antitumor-antibiotic drug isolated from soil bacterium Streptomyces, which exhibits broad-spectrum pharmacological and biochemical effects. In this study, dactinomycin was successfully labeled with technetium-99m for early diagnosis of bacterial infection and to discriminate it from acute inflammation. MATERIALS AND METHODS: Various labeling parameters such as pH, ligand concentration, reducing agent, and stabilizing agent were investigated. Radio-TLC technique was used to calculate percent radiochemical purity of radiopharmaceutical. Characterization studies were carried out using electrophoresis and radio-high-performance liquid chromatography techniques. Furthermore, saline and serum stability studies were performed to investigate biocompatibility. Biodistribution and scintigraphy studies were performed in infected and inflamed animal models to discriminate between bacterial infections (Escherichia coli and Staphylococcus aureus) and acute inflammations (heat-killed S. aureus). RESULTS: The results demonstrated that the highest radiochemical purity of at least 95% was achieved using 100-500 µg ligand and 3-8 µg SnCl2·2H2O as reducing agent at 4-9 pH. Technetium-99m-dactinomycin (Tc-DTN) was observed clearly bounded to the infection site having target/nontarget ratio 2.96±0.64 at 30 min after administration, which increased to 5.21±1.03 at 4 h after administration. Further accumulation was seen in heart, lungs, liver, stomach, kidneys, spleen, and intestine. An in-vitro cell-binding study was also performed, which showed high binding affinity of Tc-DTN with S. aureus-induced infectious lesions. CONCLUSION: Tc-DTN can easily be synthesized using standardized optimization conditions. The radiopharmaceutical has the highest accumulation potential at targeted site induced by S. aureus without any prominent in-vivo cytotoxicity. Tc-DTN may be used as a potential diagnostic agent to locate S. aureus-induced infection lesions at an early stage. Tc-DTN can successfully discriminate between infection and inflammatory models which cannot be achieved from other radiopharmaceuticals developed in the past few decades.

(177) Lu-5-Fluorouracil a potential theranostic radiopharmaceutical: radiosynthesis, quality control, biodistribution, and scintigraphy.

The aim of this study is to develop (177) Lu-5-Flourouracil as a potential cancer therapeutic radiopharmaceutical. 5-Flourouracil (5-FU) is widely accepted as an anticancer drug of broad spectrum fame. The labeling of 5-FU was carried out at different set of experimental conditions using high specific activity of (177) LuCl3 . The optimum conditions for maximum radiochemical yield was set: 5-FU (5 mg), (177) LuCl3 (185 MBq), diethylenetriaminepentaacetic acid (10 µg), reaction volume (2 mL), pH (5.5), temperature (80°C), and reaction time (20 min). The radiochemical labeling was assessed with Whatman No. 2 paper, instant thin layer chromatographic, and radio-HPLC, which revealed >94% labeling results with sufficient stability up to 6 h. Serum stability study also showed (177) Lu-5-FU promising stability. Biodistribution study in normal rats and rabbits showed liver, stomach, kidney, and heart as area of increased tracer accumulation just after injection, which decreased to 1.4%, 0.4%, 0.2%, and 0.39% ID/g, respectively, after 72 h. Glomerular filtration rate and cytotoxicity study results of (177) Lu-5-FU showed it had no adverse effect on renal function and nontoxic to blood cells. The promising characteristics of (177) Lu-5-FU, that is, clever elimination from kidney and nontoxic nature toward blood cells make it the radiopharmaceutical for further testing in patients for therapeutic purposes.