@article {Liu582, author = {Xinrong Liu and Yi Wang and Kayoko Nakamura and Sumi Kawauchi and Ali Akalin and Dengfeng Cheng and Ling Chen and Mary Rusckowski and Donald J. Hnatowich}, title = {Auger Radiation{\textendash}Induced, Antisense-Mediated Cytotoxicity of Tumor Cells Using a 3-Component Streptavidin-Delivery Nanoparticle with 111In}, volume = {50}, number = {4}, pages = {582--590}, year = {2009}, doi = {10.2967/jnumed.108.056366}, publisher = {Society of Nuclear Medicine}, abstract = {When antisense oligomers are intracellular, they migrate to and are retained in the nucleus of tumor cells and therefore may be used to carry Auger electron{\textendash}emitting radionuclides such as 111In for effective tumor radiotherapy. Methods: Our nanoparticle consists of streptavidin that links 3 biotinylated components: the antiHer2 antibody trastuzumab (to improve pharmacokinetics), the tat peptide (to improve cell membrane transport), and the 111In-labeled antiRIα messenger RNA antisense morpholino (MORF) oligomer. Results: As evidence of unimpaired function, tumor cell and nuclear accumulations were orders of magnitude higher after incubation with 99mTc-MORF/tat/trastuzumab than after incubation with free 99mTc-MORF and significantly higher with the antisense than with the sense MORF. In mice, tumor and normal-tissue accumulations of the 99mTc-MORF/tat/trastuzumab nanoparticle were comparable to those of free 99mTc-trastuzumab, confirming the improved pharmacokinetics due to the trastuzumab component. Although kidneys, liver, and other normal tissues also accumulated the nanoparticle, immunohistochemical evaluation of tissue sections in mice receiving the Cy3-MORF/tat/trastuzumab nanoparticle showed evidence of nuclear accumulation only in tumor tissue. In a dose escalation study, as measured by the surviving fraction, the nanoparticle significantly increased the kill of SK-BR-3 breast cancer Her2+/RIα+ cells, compared with all controls. Conclusion: Significant radiation-induced antisense-mediated cytotoxicity of tumor cells in vitro was achieved using an Auger electron{\textendash}emitting antisense MORF oligomer administered as a member of a 3-component streptavidin-delivery nanoparticle.}, issn = {0161-5505}, URL = {https://jnm.snmjournals.org/content/50/4/582}, eprint = {https://jnm.snmjournals.org/content/50/4/582.full.pdf}, journal = {Journal of Nuclear Medicine} }