Conjugation of phenyl isothiocyanate derivatives of carborane to antitumor antibody and in vivo localization of conjugates in nude mice.

A systematic study of the conjugation of 1-(p-isothiocyanatophenyl)-1,2-dicarba-closo-[2-3H]dodeca borane(12), 3H-1, and 7-(p-isothiocyanatophenyl)dodecahydro-7,8-dicarba-nido -[8-3H] undecaborate(1-)ion, 3H-2, to the murine monoclonal anti-CSAp antibody, Mu-9, was carried out to compare charged and uncharged boron cages in their effect upon antibody loading. Approximately one neutral cage and four of the anionic cages were successfully linked to antibody in two separate conjugates which were subsequently radioiodinated and evaluated in vivo. No significant loss of the antibody or its immunoreactivity was observed in either case. In nude mice bearing GW-39 tumor xenografts the conjugate containing the anionic carborane derivative showed a reduced tumor uptake although the tumor:non-tumor ratio was similar to that of the native antibody. The carborane cage in 2 was radiolabeled with 125I followed by attempts to purify and conjugate product 4 to a model goat IgG protein. This exploratory conjugation study was undertaken as a prelude to linking new conjugation reagents, which contain multiple anionic boron cages, to antitumor antibodies. The latter conjugates are required to maximize boron loading for the purpose of neutron-capture therapy.