Synthesis and evaluation of an 125I-labeled azide prosthetic group for efficient and bioorthogonal radiolabeling of cyclooctyne-group containing molecules using copper-free click reaction

Herein we report the radiosynthesis of a pyridine derived azide prosthetic group for iodine radioisotope labeling of dibenzocyclooctyne (DBCO) conjugated molecules. The radiolabeling of the stannylated precursor 2 was conducted using [125I]NaI and chloramine-T to give 125I-labeled azide ([125I]1) with high radiochemical yield (72 ± 8%, n = 4) and radiochemical purity (>99%). Using 125I-labeled azide ([125I]1), cyclic RGD peptide and near infrared fluorescent molecule were efficiently labeled with modest to good radiochemical yields. The biodistribution study and SPECT/CT images showed that [125I]1 underwent rapid renal clearance. These results clearly demonstrated that [125I]1 could be used as an useful radiotracer for in vivo pre-targeted imaging as well as efficient in vitro radiolabeling of DBCO containing molecules.

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