Liu, XinrongWang, YiNakamura, KayokoKawauchi, SumiAkalin, AliCheng, DengfengChen, LingRusckowski, MaryHnatowich, Donald J.2022-08-232022-08-232009-04-012015-01-28J Nucl Med. 2009 Apr;50(4):582-90. doi: 10.2967/jnumed.108.056366. Epub 2009 Mar 16.<a href="http://dx.doi.org/10.2967/jnumed.108.056366">Link to article on publisher's site</a>.0161-5505 (Linking)10.2967/jnumed.108.05636619289423https://hdl.handle.net/20.500.14038/47994<p>At the time of publication, Kayoko Nakamura was not yet associated with the University of Massachusetts Medical School.</p>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-emitting radionuclides such as (111)In 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 (111)In-labeled antiRIalpha 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 (99m)Tc-MORF/tat/trastuzumab than after incubation with free (99m)Tc-MORF and significantly higher with the antisense than with the sense MORF. In mice, tumor and normal-tissue accumulations of the (99m)Tc-MORF/tat/trastuzumab nanoparticle were comparable to those of free (99m)Tc-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+/RIalpha+ cells, compared with all controls. CONCLUSION: Significant radiation-induced antisense-mediated cytotoxicity of tumor cells in vitro was achieved using an Auger electron-emitting antisense MORF oligomer administered as a member of a 3-component streptavidin-delivery nanoparticle.en-USAnimalsCell Line, TumorCell SurvivalDNA, AntisenseDrug CarriersFemaleIndium RadioisotopesMiceMice, NudeNanoparticlesNeoplasmsRadiopharmaceuticalsStreptavidinTreatment Outcomeantisense oligomerdelivery nanoparticleradiotherapyAuger electron–emitting radionuclidestreptavidinNanomedicineNeoplasmsRadiochemistryRadiologyTherapeuticsJournal Articlehttps://escholarship.umassmed.edu/radiology_pubs/1016574740radiology_pubs/101