Metabolism of I-131-meta-iodobenzylguanidine (MIBG) in humans

I-131-MIBG is used to image and treat human pheochrmocytoma. As part of a pharmacodynamic study, the authors have evaluated its excretion and metabolism in 8 pheochromocytoma patients undergoing MIBG therapy. Following diagnostic doses (0.42-0.53 mCi) of I-131-MIBG given prior to therapy, 40-55% of the administered radioactivity appears in the urine within 24 h with 70-90% recoverable within 4 days. HPLC was used to identify potential metabolites following therapeutic doses (130-213 mCi) of I-131-NIBG. Aliquots of daily urine samples were prepared for HPLC analysis by passage through C-18 Sep-pak cartridges. A reverse-phase HPLC system (..mu..Bondapak C-18; 0.2 M ammonium phosphate/THF, 80/20) with both ultraviolet (254 nm) and radioactive (Flo-one detector, solid scintillant cell) detection was used. Radioactive metabolites were identified by co-chromatography with authentic compounds at elution solvent pH's of 4.6 and 7.0. Unaltered I-131-MIBG was the primary radioactive urinary component in all 8 patients studied, representing 74-90% of the total recovered. Two ''major'' metabolites were identified: I-131-iodide and I-131-m-iodohippuric acid, representing, respectively, 2-6% and 2-16% of the total urinary radioactivity. Of 4 additional ''minor'' metabolites (< 2% of total urinary radioactivity) detected, 2 have been identified: I-131-4-hydroxy-MIBG and I-131-m-iodobenzoic acid. The 4-5 day metabolism profiles varied from patient to patientmore » but did not change in 2 patients given 2 therapy doses 4 months apart. No obvious correlation was observed between the presence of metabolites and the location of the tumors or the plasma or urinary catecholamine levels. I-131-MIBC is a rapidly excreted, relatively stable radiopharmaceutical agent.« less