Abstract: We report a facile and effective method for radioiodine-labeled radiopharmaceuticals via copper (I)-catalyzed click
chemistry route. In the novel radioiodination method, 5-iodo (125/131I)-1, 2, 3-triazoles were synthesized after a 24-h click reaction
in organic solvent with a radiochemical yield of 13% . However, in the aqueous phase, the radiochemical yield of the
conjugation radioiodine to RGD via click chemistry was 0. This suggested an exchange between hydrogen ion and iodine ion in
aqueous phase so that no enough radioiodine was left to conjugate with RGD. We propose different mechanisms of Cu
(I)-catalyzed cycloaddition of organic azides and 1-iodoalkynes in organic phase and aqueous phase.