Influence of two transfectors on delivery of 99mTc antisense DNA in tumor-bearing mice.
OBJECTIVE
The aim of the study is to determine whether delivery into tumor cells in vivo of a 99mTc-labeled antisense phosphorothioate DNA targeting the mdr1 mRNA improves after electrostatic complexation with the transmembrane transfector (TF) carriers Neophectin or jetPEI as was observed by us in vitro.


METHODS
The biodistribution of the labeled antisense DNA before and after complexation with either TF was determined in nude mice bearing KB-G2 (Pgp++) tumors.


RESULTS
Complexation with either TF resulted in significantly higher background radioactivity levels in almost all normal tissues and modest improvement in tumor accumulation at best. The tumor accumulation was lower compared to naked at six hours (0.34 and 0.23 vs. 0.40% ID/g) and modestly higher at 24-28 hours (0.15 and 0.15 vs. 0.12% ID/g) for Neophectin and jetPEI, respectively. That blood was less than 0.18% ID/g for both TFs even at six hours suggests that tumor accumulations may have suffered from rapid blood clearance.


CONCLUSIONS
The results of this investigation show that because of the unfavorable pharmacokinetics of radiolabeled phosphorothioate DNAs when electrostatically complexed to jetPEI or Neophectin, neither TF appears to be useful in vivo despite favorable results in vitro. Future studies will devote greater consideration to the relative rates of tumor accumulation and blood clearance.
Department of Radiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. kumako@sc.itc.keio.ac.jp
Kayoko
K
Nakamura
Yi
Y
Wang
Xinrong
X
Liu
Atsushi
A
Kubo
Donald J
DJ
Hnatowich
D000818:Animals; D016373:DNA, Antisense / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D015316:Genetic Therapy; D006801:Humans; D007624:KB Cells; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000235:genetics* / Q000628:therapy*; D015609:Organotechnetium Compounds / Q000378:metabolism*; D054735:Phosphorothioate Oligonucleotides / Q000008:administration & dosage
D016373:DNA, Antisense; D015609:Organotechnetium Compounds; D054735:Phosphorothioate Oligonucleotides