[Experimental study of 99mTc-antisense DNA for tumor imaging].
This study was performed to explore the feasibility of antisense imaging with radiolabeled antisense oligonucleotides DNA in tumored nude mice in vivo. Two different tumor cell lines, KB-G2 and KB-31,were used; both antisense and control sense DNAs were administrated intratumorally. The hybridization activities analysis of MAG3 conjugated DNAs oligonucleotides was demonstrated by Polyacrylamide Gel Electrophoresis. The whole body imaging was performed 22 h after administration of radiolabeled antisense and control sense DNAs at 1.0 microg DNAs (100 microCi) in 100 microl per animal. Then the animals were sacrificed at 24 h after administration and the organs and tissues were dissected and weighed; the radioactivity of each sample was detected by r-counter; injection dose percentage per gram tissue (%ID/g) was calculated and the biodistribution obtained. Both MAGS conjugated oligonucleotides DNAs and natural oligonucleotides DNAs have the same hybridization activities. The whole body images demonstrate improved targeting of antisense DNAs vs sense DNAs in the KB-G2 but not the KB-31 animals. Tumor levels in the KB-G2 animals were significantly higher for the antisense DNAs vs sense DNAs (14.7 vs 8.5% ID/g) while this difference (8.6 vs 4.3% ID/g) was insignificant in the KB-31 animals. Evidence for tumor targeting in vivo by an antisense in that mechanism has been obtained; statistically higher tumor accumulations of the 99mTc-antisense DNA were observed when compared to the control 99mTc-sense DNA. The successful localization of antisense DNA in tumor demonstrates that antisense tumor targeting in vivo is feasible even though improvement in tumor delivery and normal tissue clearance are needed for practical antisense imaging.
Fan
Chengzhong
C
Department of Nuclear Medicine, West China Hospital, Sichuan University, Chengdu 610041, China. Chengzhong.fan@yahoo.com
Hnatowich
D J
DJ
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging* / Q000473:pathology; D004151:Dipeptides; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D051379:Mice; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D020319:Oligodeoxyribonucleotides, Antisense / Q000008:administration & dosage / Q000235:genetics; D009942:Organometallic Compounds; D011877:Radionuclide Imaging; D014407:Tumor Cells, Cultured
D004151:Dipeptides; D020319:Oligodeoxyribonucleotides, Antisense; D009942:Organometallic Compounds; C510949:technetium 99m mercapto-acetyl diglycine