UCSF

The aims of this project are to develop a new general method of nucleophilic radioiodination for aromatic tracers and to apply this method for the synthesis of radiolabeled metaiodobenzylguanidine (MIBG). MIBG is a radiolabeled pharmaceutical similar in structure to noradrenaline. The compound localizes to adrenergic tissues and can be used to image and treat neuroendocrine tumors overexpressing the human norepinephrine transporter (hNET). When labeled with I-131, MIBG can be used therapeutically to eradicate tumor cells that take up and metabolize norepinephrine. Preliminary studies with stable I-127 have shown that asymmetrical diaryliodonium salts can be iodinated with high yields. With this approach, it is possible to produce radiolabeled MIBG by using a protected diaryliodonium precursor. The effects of reaction pH, labeling solution, deprotection time, and HPLC solvent were examined for this reaction. It was found that acidic conditions gave the best labeling yields. Reaction for 7 minutes was found to be sufficient to fully deprotect the product and a labeling solution containing both CH3CN and toluene was determined to give the best total yield. HPLC was used for separation of MIBG from side-products iodoanisole and metachlorobenzylguaniine (MCBG). Removal of precursor before deprotection was also found to increase specific activity 8-fold. These results show that iodonium chemistry is a novel and effective method for radioiodinating aromatic tracers and that this method may be applied to label other radioiodine compounds.