Abstract
Purpose
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.
Conclusion
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.
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Abbreviations
- DNA:
-
deoxyribonucleic acid
- TF:
-
transfectors
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Acknowledgments
The authors wish to thank Dr. I. Sugawara (Research Institute of Tuberculosis, Tokyo, Japan) for providing the KB-G2 cell line for this investigation. This research was supported in part by the Office of Science (BER), US Department of Energy, Grant No. DE-FG02-03ER63602) and the Grant-in-Aid for Scientific Research (16591225, 17659374) and the 21st Century Center of Excellence (COE) Program entitled “Establishment of individualized cancer therapy based on comprehensive development of minimally invasive and innovative therapeutic methods (Keio University)” from the Japanese Ministry of Education, Science, Sports and Culture.
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Nakamura, K., Wang, Y., Liu, X. et al. Influence of Two Transfectors on Delivery of 99mTc Antisense DNA in Tumor-Bearing Mice. Mol Imaging Biol 8, 188–192 (2006). https://doi.org/10.1007/s11037-006-0035-6
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DOI: https://doi.org/10.1007/s11037-006-0035-6