Labeling of epirubicin with technetium-99m: Optimization, biodistribution and scintigraphic imaging in tumor bearing mice

Epirubicin is an antineoplastic agent of anthracycline antibiotic, used for treating a variety of tumor types such as lymphoma, cancer of the breast, lung, ovary and stomach. The objective of this work was to demonstrate direct radiolabeling of epirubicin with ^99mTc, quality control, biological characterization and scientigraphic evaluation in tumor bearing mice. The 99mTc-epirubicin labeling was optimized by varying the amounts of ligand 100-350μg, stannous chloride dihydride 20-50μg and pH range 2-10 by using NaOH or HCl. The radiochemical purity of ^99mTc-epirubicin was evaluated by chromatographic techniques (Whatman No. 3 paper and ITLC-SG). HPLC analyses were performed to check purity of epirubicin and radiochemical purity of labeled ^99mTc- epirubicin. Biodistribution and scintigraphic imaging of ^99mTc-epirubicin was performed in normal and tumor bearing mice at various time intervals. The optimum conditions ensuring ^99mTc-epirubicin labeling yield as high as 99% by adding 35μg SnCl₂.2H₂O, 200μg of ligand at pH 6 for 30 min at room temperature (25°C±2°C). HPLC of ^99mTc-epirubicin shows about 99% binding of the compound with technetium-99m. Electrophoresis study indicated the neutral nature of ^99mTc-epirubicin. Biodistribution data and scintigraphic results showed that ^99mTc-epirubicin accumulated in the liver as well as in tumor with significant uptake and excellent retention. ^99mTc-epirubicin shows good stability in human serum. In vitro and in vivo studies revealed the significantly uptake of ^99mTc-epirubicin in the tumor, and also indicating the efficiency of ^99mTc-epirubicin as a tumor diagnostic agent.