Astatine-211 is of high interest in development of targeted therapeutic radiopharmaceuticals. However, in vivo instability of astatinated biomolecules has been problematic. We have evaluated a number of bioconjugation reagents designed to circumvent the in vivo instability, including several that contain aromatic boron cage moieties. Those studies demonstrated that reagents containing a closo-decaborate(2-) moiety provide biomolecule labeling that is stable to in vivo deastatination. A number of bioconjugation reagents containing the closo-decaborate(2-) moiety have been developed to prepare monoclonal antibody (mAb) conjugates. Importantly, those conjugates can be astatinated directly in high yields. Unfortunately, the unique nature of the dianionic decaborate(2-) moiety can also introduce undesirable in vivo characteristics. Thus, modifications in the reagents have been made to keep them from localizing in kidneys or liver, and to change the pharmacokinetics of the labeled biomolecule. Examples of the development and applications of several At-211 labeling reagents will be given in this presentation.

Development of bioconjugation reagents for labeling biomolecules with astatine-211

243rd National Meeting (2012)

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