Efficient and Site-Specific (125)I-Radioiodination of Bioactive Molecules Using Oxidative Condensation Reaction

[Image: see text] In this report, the novel and site-specific radioiodination of biomolecules by using aryl diamine and alkyl aldehyde condensation reaction in the presence of a Cu(2+) catalyst under ambient conditions was reported. (125)I-labeled alkyl aldehyde was synthesized using a tin precursor with a high radiochemical yield (72 ± 6%, n = 5) and radiochemical purity (>99%). The utility of the radioiodinated precursor was demonstrated through aryl diamine-installed c[RGDfK(C)] peptide and human serum albumin (HSA). Radioiodinated c[RGDfK(C)] peptide and HSA protein were synthesized with high radiochemical yields and purity. (125)I-HSA protein showed excellent in vivo stability and negligible thyroid uptake as compared with directly radioiodinated HSA by using the tyrosine group. Excellent reaction kinetics and the in vitro and in vivo stabilities of (125)I-labeled alkyl aldehyde have suggested the usefulness of the strategy for the radioiodination of bioactive molecules.