211At and 125I-Labeling of (Hetero)Aryliodonium Ylides: Astatine Wins Again

Despite the growing interest in radioiodine and At-211-labeled radiopharmaceuticals, the search for radiolabeling reactions has been somewhat neglected, resulting in a limited number of available radiosynthetic strategies. Herein we report a comparative study of nucleophilic I-125 and At-211-labeling of aryliodonium ylides. Whereas radioiodination efficiency was low, At-211-labeling performed efficiently on a broad scope of precursors. The most activated aryliodonium ylides led rapidly to quantitative reactions at room temperature in acetonitrile. For deactivated precursors, heating up to 90 degrees C in glyme and addition of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) as radical scavenger appeared essential to avoid precursor degradation and to achieve high radiochemical yields and molar activity. The approach was applied successfully to the preparation of 4-[At-211]astatophenylalanine (4-APA), an amino acid derivative increasingly studied as radiotherapeutic drug for cancers. This validated aryliodonium ylides as a valuable tool for nucleophilic At-211-labeling and will complement the short but now growing list of available astatination reactions.

Automated summary

Despite the growing interest in radioiodine and At-211-labeled radiopharmaceuticals, the research on radiolabeling reactions has been neglected, resulting in limited available synthetic strategies. This study compared the nucleophilic I-125 and At-211 labeling of aryliodonium ylides, and found that At-211 labeling was efficient on various precursors. The activation state of the aryliodonium ylides and reaction conditions played important roles in achieving high radiochemical yields and molar activity.