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.