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[Study on the biological character of liposome-mediated 99m-technetium labeled antisense oligonucleotide for c-myc
Jianguo Zheng1, Tianzhi Tan, Yunchun Li
1Department of Nuclear Medicine, West China Hospital, Sichuan University, Chengdu 610041, China.
Objective:
To probe the biological character of liposome-mediated 99m-technetium-labeled antisense oligonucleotide of c-myc mRNA, and lay the foundations for clinical research on antisense image or treatment.
Methods:
Antisense, sense and scrambled oligonucleoyide, each containing 15 bases, were synthesized elsewhere. The rates of liposome-entrapped 99mTc-DNA and 99mTc-DNA combination with plasma protein were tested through trichloroacetic acid precipitation. BALB/c mice were used to test the biodistribution in vivo, and rabbits were used to investigate the pharmacokinetics characters.
Results:
Their rates of combination with plasma protein ranged from 34.81% to 70.53%. Reticuloendothelial system played an important role in the biodistribution; stomach, blood and intestines were less important; other tissues accumulated the least of the liposome-mediated 99mTc-labeled c-myc oligonucleotides. The pharmacokinetics of liposome-entrapped 99mTc-DNA fitted the open dithecal model. Their distribution (t1/2 alpha) half time was about 2 to 5 minutes, and clearance (t1/2 beta) half time about 100 to 150 minutes. Plasma clearance was smaller than 2 ml/min.
Conclusion:
The rate of 99mTc-DNA combination with plasma protein was high. The biological half time of liposome-mediated 99mTc-DNA was proper. Plasma clearance was high. So liposome-mediated 99mTc-DNA is a potential kind of radioactive agent.
