[211At]Astatine-Labeled Compound Stability: Issues with Released [211At]Astatide and Development of Labeling Reagents to Increase Stability

D.   Scott   Wilbur

doi:10.2174/1874471010801030144

Abstract

A review of the literature has been conducted on 211At-labeled compounds, which focuses on their in vitro and in vivo stability towards deastatination. In vivo stability is very important in 211At-labeled compounds being developed for treating human disease. Instability of the 211At-carbon bond found in many labeled compounds leads to release of [211At]astatide. Therefore, the review includes information from literature reports on toxicity resulting from free [211At]astatide in animal models. The review also examines 211At-bond stability obtained when using different methods or reagents to label a variety of large and small molecules. Fortunately, in vivo stability is readily determined by conducting coinjected dual-label studies, where the study compound is labeled with [125/131I]radioiodine and separately with [211At]astatine. Radionuclide concentrations in selected tissues (i.e. lung, spleen, thyroid or neck, stomach) from several literature reports have been plotted to provide a visual indicator of relative in vivo stability obtained from the various labeling approaches. When the labeling approach involves formation of a carbon-astatine bond, a major factor determining stability appears to be the rate of metabolism of the carrier molecule. Other factors such as charge on the molecule, electronic and steric encumbrance about the astatine, and use of non-metabolizable (D-) forms of amino acids may also contribute to in vivo stability, but these could not be delineated from the literature reports. An alternate 211At-labeling approach, where a B-At bond is formed on anionic aromatic boron cage moieties, appears to increase stability to in vivo deastatination.

Keywords: Astatine-211, radiolabel stability, deastatination, alpha-therapy, endoradiotherapy, targeted radiotherapy, radioimmunotherapy, radiolabeling