Influence of two transfectors on delivery of 99mTc antisense DNA in tumor-bearing mice

Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging
Kayoko NakamuraDonald J Hnatowich

Abstract

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

References

Jul 1, 1997·Nuclear Medicine and Biology·P WinnardD J Hnatowich
Sep 20, 2000·Bioconjugate Chemistry·C H Tung, S Stein
Jan 5, 2002·Cancer Biotherapy & Radiopharmaceuticals·Y M ZhangD J Hnatowich
Jul 18, 2002·Bioconjugate Chemistry·Guozheng LiuDonald J Hnatowich
Sep 23, 2003·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Yu-Min ZhangDonald J Hnatowich
Nov 18, 2004·Bioconjugate Chemistry·K NakamuraD J Hnatowich
Mar 17, 2005·Bioconjugate Chemistry·Xiankai SunJohn-Stephen Taylor

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Citations

Aug 23, 2006·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Xinrong LiuDonald Hnatowich
Feb 26, 2010·Nucleosides, Nucleotides & Nucleic Acids·James A H InksterThomas J Ruth
Nov 3, 2009·Cancer Biotherapy & Radiopharmaceuticals·Yi WangDonald J Hnatowich

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