Study of Pharmacokinetic Properties for ~(99m)Tc-MAG_3-ASON / 重庆医科大学学报

Objective: To study the pharmacokinetic properties of 99mTc-labeled chelic polymer of MAG3-ASON.Methods: Chelic polymer of 99mTc-MAG3-ASON was prepared according to former methods.Subsequently,this chelic polymer change of concentration was determined by radioactivity counts per minute(CPM),and its half-life of distribution(T1/2?),the half-life of elimination(T1/2?),the central compartment volume of distribution(Vc),the total apparent volume of distribution(Vd) and the total rate of clearance(CL) were calculated by means of 3P97 software.Finally,its rate of binding to serum protein was measured by trichloroacetic acid precipitation.Results: The T1/2?,the T1/2?,the Vc,the Vd and the CL were 2.11min,95.19min,114.9ml,2430.8ml and 17.7ml/min,respectively.After being incubated with fresh human serum for 1.5h,its rate of binding to serum protein was 11.82%.Conclusion: The process of transportation for chelic polymer of 99mTc-MAG3-ASON in vivo is consistent with two-compartment model and it has desirable pharmacokinetic properties.Therefore,it may be used for diagnostic imaging and therapy of cancer.

Preparation of ~(99m) Tc-MAG_3-ASON and distribution in breast carcinoma-bearing nude mouse model / 重庆医科大学学报

Objective:To discuss the preparation of ~(99m) Tc-labelled antisense oligonucleotide (ASON) and its distribution in breast carcinoma-bearing nude mouse model.Methods:N-hydroxysuccinimide ester of mercaptoacetylglycylglycylglycine (NHS-MAG_3) was synthesized by one step.A 15-mer single-stranded phosphorothioate ASON complementary to c-erbB2 oncogene mRNA was coupled with NHS-MAG_3 and labelled with ~(99m) Tc subsequently.~(99m)Tc-MAG_3-ASON was purified on a gel filtration column of Sephadex G25,then its stability was evaluated,and finally the distribution was detected in breast carcinoma-bearing nude mice model.Results: The average labeling efficiency of 99mTc-MAG_3-ASON was 70.6%,and the radiochemical purity was 94.3% after being labelled at room temperature for 4h. When incubated with fresh human serum, the radiochemical purity of ~(99m) Tc-MAG_3-ASON was 93.8%. The serum protein binding of ~(99m) Tc-MAG_3-ASON was 11.8%.The highest uptake of breast carcinoma was 6.09%ID/g at 2hs.Conclusion:~(99m)Tc-MAG_3-ASON has desirable stability,higher uptake in breast carcinoma and may provide a new sensitive tool for diagnostic imaging and therapy for breast carcinoma in the future.