Radioactive iodine exchange reaction of HIPDM: Kinetics and mechanism

HIPDM is a lipid-soluble diamine which crosses the blood brain barrier and displays a long brain retention time. In conjunction with single photon emission computed tomography (SPECT), I-123 HIPDM has been applied clinically for studying regional cerebral perfusion. Labeling of HIPDM with radioactive iodine is simple and amenable to a kit form. In spite of the simplicity of the exchange reaction, occasionally the reaction may show low labeling yield with no apparent explanation for the failure, especially when pure (p,5n) I-123 sodium iodide was used. The authors have found that in the presence of a small amount of reducing agent, sodium bisulfite (20 μg/ml), lowered the labeling yield (from 98% to 1%), while an oxidizing agent iodate (50 μg/ml) enhanced the yield and reaction rate. The mechanism of this exchange reaction probably involves the initial formation of an electrophilic intermediate, I/sup +/. Trace metal ions (Fe/sup +3/, Al/sup +3/, Zn/sup +2/, Mg/sup +2/, Ni/sup +2/) showed negligible effects, but Cu/sup +2/ ion lowered the labeling yield (from 98% to 92%). In order to study this reaction further, they have investigated systematically the kinetics and mechanism. The exchange reaction is temperature dependent, and the graph of ln(1-F) vs. time at various temperatures (400 to 1000C) showed linear relationship, indicative of a simple isotope exchange reaction (optimal reaction condition: pH 2-3, heating at 1000C for 30 min.). By using a sodium iodide carrier-added reaction and measuring the reaction rate at three different temperatures, the activation energy for this exchange reaction is determined: Ea = 30.6 Kcal/mole. This information may be helpful in understanding the exchange reaction of HIPDM and other molecules labeled by the same type of iodine exchange reaction