Synthesis and evaluation of an¹²⁵I-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 give¹²⁵I-labeled azide ([¹²⁵I]1) with high radiochemical yield (72 ± 8%, n = 4) and radiochemical purity (>99%). Using¹²⁵I-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.