Efficient Radiohalogenation of Aromatic Rings for Nuclear Medicine

Background & Unmet Need

• Demand for novel radiopharmaceuticals for imaging and radiotherapy has rapidly increased, with over 2 million PET scans and about 20 million nuclear medicine procedures performed annually in the US
• Halogen radioisotopes are essential for diagnostic imaging and research due to their ideal chemical properties and nuclear decay characteristics
• Traditional radiolabeling methods require high temperatures, result in modest yields, necessitate extensive purification to remove toxic reagents, and have limited substrate scope for aromatic rings
• Newer approaches which would enable radiolabeling of aromatic rings suffer from limited functional group tolerance, need for extensive purification, instability, and poor labeling of sterically hindered positions
• Unmet Need: More efficient, versatile, and reliable radiolabeling methods, particularly for challenging substrates and positions

Technology Overview

• The Technology: Method for rapid and quantitative radiohalogenation of aryl and heteroaryl rings at room temperature by reductive elimination from bismuth complexes
• This method enables regioselective radiohalogenation of electron-rich, electron-deficient, and/or sterically hindered (hetero)aryl rings with nearly quantitative halide incorporation and reaction times of less than 30 minutes
• PoC Data: The inventors performed bismuth-mediated radiohalogenation of aryl boronic acids and aryl tetrafluoroborates with Na[125I]I and Na[211At]At at room temperature and with NH4[77Br]Br at 80 °C in mild conditions with 35-99% radiochemical conversion
• The method has also been used to synthesize [124I]MIP-1095 and [124I]MIBG with high radiochemical yield, high molar activity, and >99 percent radiochemical and chemical purity

Technology Applications

• Radioiodination (131I, 125I, and 124I), radiobromination (76Br and 77Br), or radioastatination (211At) of a range of electron-deficient, -neutral, and -rich, sterically crowded aryl and heteroaryl rings
• Use for generation of radiopharmaceuticals for molecular imaging or radiotherapy applications

Technology Advantages

• Bismuth precursors are stable at room temperature and resistant to light and moisture
• Enables easy purification from non-labeled impurities
• Bismuth is non-toxic to human cells, reducing risks from contamination 
• Method tolerates a wide variety of functional groups
• Reactions are successful even when the halide is present in 1000-fold stoichiometric deficit