In Vivo Stability Improvement of Astatobenzene Derivatives by Introducing Neighboring Substituents

211At is a promising radiohalogen for targeted
α
therapy. However, some astatinated compounds undergo deastatination
in vivo, leading to unintended astatine accumulation in nontarget
tissues. Recently, a group reported that the in vivo stability of
an astato group on an alkyl group could be improved by placing specific
substituents around the astato group. We hypothesized that such an
approach could be applied to improve the stability of an astato group
on aromatic groups. We designed and synthesized astatobenzene derivatives
with neighboring substituents with different physical properties.
In vitro and in vivo stabilities of these derivatives were evaluated
by comparing with corresponding radioiodinated analogues. Notably,
a derivative with two ortho dimethylcarbamoyl substituents significantly
improved the stability of the astato group. This study supports the
notion that strategic structural modification of substituents adjacent
to an astato group can enhance its in vivo stability, potentially
leading to the development of effective 211At-labeled radiopharmaceuticals.