Synthesis, characterization and radiolabeling of DTPA-doxorubicin complex with 68Ga

1200 Objectives To synthesize and characterize the conjugate of doxorubicin with cyclic diethylenetriaminepentaacetic acid anhydride (DTPA) and radiolabel the resultant complex with 68Ga. Methods A DTPA-doxorubicin complex was synthesized by conjugation of doxorubicin with acylated DTPA. 200 mg (0.56 mmol) of cyclic DTPA anhydride was dissolved in 2 ml of dichloromethane followed by addition of 100 μl α,α-dicholoromethyl methyl ether and mixture was stirred up to 60 min at room temperature. The excess of chlorinating agent was evaporated under vacuum. 160 mg of doxorubicin was dissolved in 3 ml of dimethylfuran and added to the acylated DTPA. The mixture was stirred at room temperature for overnight. Solvent was vacuum evaporated and dark red precipitate was obtained. The formation of DTPA-doxorubicin complex was characterized by 1H-NMR, 13C-NMR. The complex was radiolabeled with 50 µCi (0.5 ml) of 68Ga in 0.1M sodium acetate buffer (pH - 5.5). The conditions for radiolabeling like temperature (300C - 900C) and incubation time (5, 10, 15, 20 min) were standardized to get maximum labeling efficiency. Results The resultant complex was radiolabeled with 68Ga and radiolabeling efficiency of about 60% was observed when incubated for 15 min at 900C. We attempted to increase the radiolabeling efficiency to more than 95% when the radiolabel was filtered through a C18-Sep-pak cartridge. Conclusions DTPA-doxorubicin complex was successfully labeled with 68Ga and can be used as a powerful PET imaging agent for early detection of cancer and treatment response monitoring to Vincristine, actinomycin-D and cyclophosphamide (VAC) regimen.