[Study on the biological character of liposome-mediated 99m-technetium labeled antisense oligonucleotide for c-myc mRNA].
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.


CONCLUSIONS
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.
Zheng
Jianguo
J
Department of Nuclear Medicine, West China Hospital, Sichuan University, Chengdu 610041, China.
Tan
Tianzhi
T
Li
Yunchun
Y
Liang
Zhenglu
Z
Zhang
Chun
C
Pan
Weiming
W
D000818:Animals; D004247:DNA / Q000378:metabolism / Q000493:pharmacokinetics*; D008081:Liposomes; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016376:Oligonucleotides, Antisense / Q000378:metabolism / Q000493:pharmacokinetics*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism / Q000493:pharmacokinetics*; D012333:RNA, Messenger / Q000378:metabolism / Q000493:pharmacokinetics; D011817:Rabbits; D013667:Technetium; D014018:Tissue Distribution
D008081:Liposomes; D016376:Oligonucleotides, Antisense; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D013667:Technetium; D004247:DNA