Boron neutron capture therapy using pre-targeting methods

A method for effecting boron neutron capture therapy (BCNT) of tumor cells in a patient, comprising the steps of:

• (A) administering to said patient a targeting composition comprising a conjugate of a first member of a specific binding pair and an antibody or antigen-binding antibody fragment, wherein said antibody or antibody fragment selectively binds to a characteristic intracellular or cell surface antigen produced by or associated with said tumor cells and present at said tumor cells, and allowing said targeting composition to localize at said tumor cells;
• (B) optionally, administering to said patient a clearing composition, and allowing said clearing composition to clear non-localized targeting composition from circulation;
• (C) administering to said patient a boron compound comprising a conjugate comprising a complementary member of said binding pair and boron atoms, and allowing said boron compound to localize at said tumor cells;
• and
• (D) irradiating the boron atoms of said boron compound localized at said tumor cells, thereby effecting BNCT of said tumor cells.

A kit suitable for use in a method for targeting boron atoms to tumor cells in a patient, the kit comprising in separate containers:

• (A) a sterile, injectable preparation of a targeting composition comprising (i) first member of a specific binding pair selected from the group consisting of a single-stranded oligonucleotide, a double-stranded oligonucleotide, an enzyme, an enzyme substrate, biotin, and avidin, wherein said biotin is provided as a biotinidase-resistant biotin analog comprising a biotin moiety bonded to an unnatural D-amino acid via a peptide bond, and (ii) an antibody or antigen-binding antibody fragment, wherein said antibody or antibody fragment selectively binds to a characteristic intracellular or cell surface antigen produced by or associated with said tumor cells and present at said tumor cells;
• (B) optionally, a clearing composition;
• and
• (C) a boron (i) a complementary member of said binding pair selected from the group consisting of a complementary single-stranded oligonucleotide, a complementary double-stranded oligonucleotide, an enzyme substrate for said enzyme, an enzyme for said enzyme substrate, avidin, and biotin, respectively, wherein said biotin is provided as a biotinidase-resistant biotin analog comprising a biotin moiety bonded to an unnatural D-amino acid via a peptide bond, and (ii) one or more addends comprising a plurality of boron atoms.

A kit suitable for use in a method for targeting boron atoms to tumor cells in a patient, the kit comprising, in separate containers:

• (A) a sterile, injectable preparation of a targeting composition comprising (i) a first member of a specific binding pair and (ii) an antibody or antigen-binding antibody fragment, wherein said antibody or antibody fragment selectively binds to an antigen produced by or associated with said tumor cells and present at said tumor cells;
• (B) a clearing composition;
• and
• (C) a boron compound comprising a conjugate comprising (i) a complementary member of said binding pair and (ii) one or more addends comprising a plurality of boron atoms.