Critical evaluation of bispecific antibodies as targeting agents for boron neutron capture therapy of brain tumors.

作者: Barth Rf , Soloway Ah , Adams Dm , Liu L , Reisfeld Ra

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摘要: Boron neutron capture therapy (BNCT) is based on the nuclear reaction that occurs when 10B, a stable isotope, irradiated with low energy neutrons to produce high linear transfer (LET) alpha particles and recoiling 7Li nuclei. In order for BNCT be successful in treating cancer, approximately 10(9) boron atoms must delivered per tumor cell sustain lethal (n,a) reaction. present study, we have produced characterized bispecific antibody (BsAbB8), which was reactive both human glioma melanoma lines, as well variety of polyhedral borane anions (PBA). The affinity constants (KA) BsAb-B8 D-54 MG M21 cells were 3.49 2.57 x 10(8) M-1, respectively, almost identical those parental mAb 9.2.27 these lines. vivo localizing properties studied nude mice bearing subcutaneous xenografts glioma. Following intravenous injection 131I-labeled BsAb-B8, 3.4 +/- 0.2% injected dose/g detected at 24 hours, then slowly declined 2.0 0.4% 96 hours compared 1.34 0.07% 0.03 0.01%, normal mouse IgG. Based assumption all antigenic receptor sites could saturated, following calculations been carried out. maximum concentration 1 g would 99.6 micrograms, bind 71.7 ng PBA. However, since least 500 more required gram 10B reaction, macromolecule containing -10(3)-10(4) rather than molecular weight PBA deliver this amount. Such macromolecules synthesized by us, future studies should provide information feasibility using them combination requisite amount 10B.

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