Radioactive iodine exchange reaction of HIPDM: kinetics and mechanism

In conjunction with single photon emission computed tomography (SPECT), iodine-123 (123I)-labeled N,N,N'-trimethyl-[2-hydroxy-3-methyl-5-iodobenzyl]-1,3-propanediamine (HIPDM) has been used clinically as a regional cerebral perfusion imaging agent. The [123I]HIPDM can be prepared by a simple aqueous exchange reaction in a kit form. We synthesized unlabeled HIPDM by condensation of 2-hydroxy-3-methyl-5-iodobezaldehyde and N,N,N'-trimethyl-1,3-propanediamine, followed by a sodium borohydride reduction reaction. The kinetics of the radioactive iodine exchange reaction for the preparation of [123I]HIDM is controlled by the pH, the temperature, and the presence of reductant (sodium bisulfite), and oxidant (sodium iodate). The reaction is a second order iodine-iodine exchange with an activation energy of 30.6 kcal/mole. The mechanism of this reaction probably involves the formation of an active 1+ or iodine free radical, which is sensitive to the presence of a reductant, such as sodium bisulfite.