Effect of Water on Direct Radioiodination of Small Molecules/Peptides Using Copper-Mediated Iododeboronation in Water-Alcohol Solvent

Direct radioiodinationof peptides using copper-mediated iododeboronationis a promising radiosynthetic method for solving issues of classicaldirect radiolabeling, such as toxicity of the organotin precursor(iododestannylation) or formation of radio byproducts (by electrophiliciodination of a tyrosine residue). However, the parameters for optimizingthe reaction conditions for various peptides are not completely understood.In particular, considering peptide solubility, the effects of water-containingsolvents on labeling efficiency should be thoroughly investigated.Herein, we describe the effect of water on copper-mediated radioiododeboronationand the key factors for ensuring the successful radiolabeling of smallmolecules and peptides in water-organic solvents. I-125-labeled substrates containing peptides ([I-125]m/p-IBTA) were obtained with high radiochemicalconversions (RCCs: >95%) using an alcohol solvent, and a decreasein these RCCs was observed with increasing water content in the methanolsolvent. Additionally, when using water-methanol solvents,a difference in RCC due to the substituent effect was also observed.However, the RCCs can be improved without the use of other additivesby adjusting the copper catalyst and time of the labeling reactionor by utilizing substituent effects. This study contributes to theimprovement of the design of boronic peptide precursors and radiolabelingprotocols using copper-mediated iododeboronation.