Comparison of Different Organometallics Towards Electrophilic Aromatic ²¹¹At‐Astatinations of Highly Reactive Tetrazines

Organometallics can be used as precursors for electrophilic ²¹¹At-statinations. In this report, we compared the potential of aryl trimethylsilanes, -germanes, or -stannanes to be used as precursors to ²¹¹At-label highly reactive tetrazines. Tetrazines can be used for pretargeted radioligand therapies or be applied as synthons to radiolabel rapidly and orthogonally a broad set of precursors such as peptides, mAbs or nanomedicines. All precursors could successfully be synthesized and radiolabeled. The reactivity of organogermanium reagents ranged between those of respective organotin and organosilicon precursors. Moreover, organogermanium reagents proved promising for accessing more complex and polar tetrazine scaffolds. In contrast to organotin derivatives, the use of protecting groups could be avoided for organogermanium and -silicon precursors. The developed ²¹¹At-labeled tetrazines could be labeled in radiochemical conversions of 60-90 %. Organogermanium and -silicon precursors were clearly advantaged as additional deprotection steps could avoided. Reported labeling procedures allow astatinations of highly reactive tetrazines to be used for pretargeted approaches or to applied as highly reactive synthons to label the next-generation of ²¹¹At-labeled radiopharmaceuticals.