High-Yield Room-Temperature Aryl ²¹¹At Radiolabeling via Redox-Activated Column-Shipped ²¹¹At

Area of Science:

• Radiochemistry
• Nuclear Medicine
• Organic Synthesis

Background:

• Targeted alpha-therapy (TAT) offers potent cancer treatment by delivering high-energy alpha particles.
• Efficient late-stage radiolabeling is crucial for developing novel TAT radiopharmaceuticals.
• Astatine-211 (At-211) is a promising alpha-emitter for TAT, but its efficient incorporation into molecules remains a challenge.

Purpose of the Study:

• To evaluate a catalyst-enabled astatodeboronation approach for late-stage At-211 labeling.
• To investigate the use of wet chemically regenerated At-211 for radiopharmaceutical development.
• To explore the scope and conditions for labeling various aryl boronic esters with At-211.

Main Methods:

• Utilized wet chemically regenerated At-211 recovered from 3-octanone-impregnated columns.
• Employed a catalyst-enabled astatodeboronation reaction for radiolabeling aryl boronic esters.
• Performed time-dependent studies to optimize reaction parameters and examined a series of substrates with diverse electronic properties.
• Applied density functional theory (DFT) calculations to analyze bonding descriptors.

Main Results:

• Achieved radiochemical conversions for aryl boronic esters ranging from 68% to 97% under mild conditions.
• Demonstrated successful late-stage labeling using regenerated At-211.
• Identified optimal reaction parameters through time-dependent studies.
• DFT calculations provided insights into B-C and At-C bonding.

Conclusions:

• Wet chemically regenerated At-211 is effective for the late-stage labeling of aryl boronic esters.
• The astatodeboronation method offers a mild and efficient route to At-211 radiopharmaceuticals.
• This work provides a foundation for further development of At-211 radiolabeling strategies for targeted alpha-therapy.