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Synthesis and preclinical evaluation of bactericidal agent isolated from soil bacterium (Streptomyces)

a novel diagnostic technique to enhance anticancer efficacy through radiosynthesis

Rizvi, Syed F.A.a,b; Tariq, Salehaa; Mehdi, Muhammada

doi: 10.1097/MNM.0000000000000916

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 (99mTc-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 99mTc-DTN with S. aureus-induced infectious lesions.

Conclusion 99mTc-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. 99mTc-DTN may be used as a potential diagnostic agent to locate S. aureus-induced infection lesions at an early stage. 99mTc-DTN can successfully discriminate between infection and inflammatory models which cannot be achieved from other radiopharmaceuticals developed in the past few decades.

aDepartment of Chemistry, Government College University, Faisalabad

bIsotope Production Division, Pakistan Institute of Nuclear Science and Technology, Islamabad, Pakistan

Correspondence to Syed F.A. Rizvi, PhD, Department of Chemistry, Government College University, Faisalabad 38000, Pakistan Tel: +92 336 786 7086; fax: +92 423 515 7233; e-mail:

Received June 21, 2018

Received in revised form August 3, 2018

Accepted August 28, 2018

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