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- W2061413376 abstract "A delivery molecule for directed boron neutron capture therapy against epidermal growth factor (EGF) receptor-rich tumors, such as gliomas, squamous carcinomas, and breast cancers, is presented. EGF and sulfhydryl boron hydride (BSH) were covalently coupled to an allylated 70 kDa dextran chain to form a conjugate. Conjugates with low and high substitution rates of BSH, as well as without BSH, were investigated. The conjugate with a low amount of boron had approximately 6 BSH (72 boron atoms) per dextran, while the conjugates with higher amounts had an average substitution of 55 BSH (660 boron atoms) per dextran. The maximum substitution of boron to dextran in a single experiment was over 800 boron atoms. Binding, retention, and internalization of 125I-labeled conjugates were investigated on cultured human glioma cells. Binding of the conjugates was EGF receptor specific, but the amount of BSH coupled to dextran affected specificity, more than the presence of dextran. The nonspecific binding of the conjugates increased with the amount of attached boron. This was partly due to nonspecific adhesion to the plastic in the culture dishes. [125I]EGF−allyldextran with 6 BSH had a binding maximum after 4 h of continuous incubation and thereafter decreased in binding, while [125I]EGF−allyldextran with the higher substitution rate had a slow increase of binding during 24 h. Over 93% of the radioactivity bound to the cells was internalized, but the retention was quite poor. Only one-third of the cell-bound activity was still associated to the cells 4 h after incubation had ended. In conclusion, it is posible to load the conjugates produced with high amounts of boron, and they retained specificity for the EGF receptor and internalized into cultured cells. Theoretical calculations show that about 103 boron atoms per EGF-based conjugate are needed to give a satisfactory therapeutic response. These conjugates are within reach of that level." @default.
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- W2061413376 date "1996-01-01" @default.
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- W2061413376 title "Development and in Vitro Studies of Epidermal Growth Factor−Dextran Conjugates for Boron Neutron Capture Therapy" @default.
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- W2061413376 doi "https://doi.org/10.1021/bc9600473" @default.
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