Delivery of boron-10 for neutron capture therapy by means of monoclonal antibody - Starburst dendrimer immunoconjugates

Using a high molecular weight macromolecule, poly-DL-lysine and a methyl isocyanato-polyhedral borane, Na(CH3)3 NB10H8NCO, the authors have prepared a boronated polylysine (BPL) containing 23% boron by weight and having > 1,700 boron atoms per polymeric unit. This boronated macromolecule was then attached to MoAbs utilizing two heterobifunctional reagents N-succinimidyl 3-(2 pyridyldithio) propionate (SPDP), which was used to introduce potential sulfhydryl groups into proteins, and sulfo m-maleimidobenzoyl-N-hydroxysuccinimide ester (sMBS), which was used to introduce maleimido groups on MoAbs. The resulting immunoconjugates retained a high degree of in vitro immunoreactivity but had lost their in vivo tumor localizing properties. It became apparent that an alternative approach was required to produce boron containing immunoconjugates that would retain both their immunoreactivity and in vivo tumor localizing properties. The purpose of the present report is to describe the most recent efforts to prepare boron containing immunoconjugates using a neutrally charged precision macromolecule consisting of repetitive polyamido amino groups (PAMAM) arranged in a starburst pattern