Technetium-99m radiolabeling through conjugation with l,l-ethylene dicysteine chelator of a trimethoxylated flavone and its bioevaluation in rat with induced C6 glioma tumor as a new cancer diagnostic agent

Abstract

Xanthomicrol (4′,5-dihydroxy-6,7,8-trimethoxyflavone) is the main active component of Dracocephalum kotschyi Boiss leaf extract. It has showed selective cytotoxic activity against some cancer cell lines and little effect on human fetal foreskin fibroblast cells used as nonmalignant control. This study aimed to develop 99mTc-labeled xanthomicrol and to evaluate its efficiency as a new tumor imaging agent. l,l-Ethylene dicysteine (EC) chelator was conjugated to xanthomicrol. EC-Xanthomicrol was labeled with technetium-99m by using tin chloride as a reducing agent and incubating at room temperature. Radiochemical purity and in vitro stability were analyzed by thin layer chromatography and high-performance liquid chromatography. In vitro cellular uptake and binding profile of radio-conjugate was determined on C6 glioma cells. In vivo bioevaluation and imaging studies of [99mTc]Tc-EC-Xanthomicrol were performed in C6 glioma tumor induced rat at different time points after injection of radio-conjugate. The high radiochemical yield (>95 %) was achieved for [99mTc]Tc-EC-Xanthomicrol which was stable up to 6 h. The radio-conjugate indicated high cell uptake (35.12 % at 2 h) which demonstrated to be specific. Tumor uptake was seen for [99mTc]Tc-EC-Xanthomicrol (1.23 ± 0.14 %ID/g) at 1 h post injection. Scintigraphy confirmed that tumors could be visualized clearly with [99mTc]Tc-EC-Xanthomicrol. The results indicated that [99mTc]Tc-EC-Xanthomicrol has potential to be considered as a new radiotracer in glioma tumor imaging.