Metabolism of iodine-131 metaiodobenzylguanidine in patients with metastatic pheochromocytoma.

Iodine-131 metaiodobenzylguanidine ([131I]MIBG) is used to image and treat human pheochromocytoma. As part of a pharmacodynamic study of this agent, we have evaluated its excretion and metabolism in nine pheochromocytoma patients undergoing MIGB therapy. Following diagnostic doses of [131I]MIBG given prior to therapy, 40 to 55% of the administered radioactivity generally appeared in the urine within 24 hr and 70 to 90% was recovered within 4 days. Reverse-phase high performance liquid chromatography was used to identify radioactive metabolites following therapeutic doses of [131I]MIBG. Unaltered [131I]MIBG was the major radioactive urinary component found, representing 75 to 90% of the total in all but one of the nine patients examined. The urine samples from the patient, whose rate of urinary excretion was the lowest of the group, contained [131I]-m-iodohippuric acid ([131I]MIHA) in amounts equal to that of [131I]MIBG, as well as small amounts of [131I]iodide and [131I]-m-iodobenzoic acid ([131I]MIBA). Iodine-131 MIHA and [131I]iodide were also minor components in the urine samples from the other eight patients. Trace quantities of [131I]MIBA and 131I-4-hydroxy-3-iodobenzylguanidine ([131I]HIBG) were also detected in a few of the patient urine samples examined. The 4- to 5-day metabolism profiles varied from patient to patient but were similar for the same patient following therapy doses given 4 mo apart. There was no obvious correlation between the presence of metabolites and the location of the tumors or the plasma or urinary catecholamine levels. Extraction of radioactivity from two pheochromocytomas removed from patients was determined to be primarily MIBG. These studies suggest that [131I]MIBG is a rapidly excreted, relatively stable radiopharmaceutical agent.