NO-CARRIER-ADDED IODINE-131-FIBG - EVALUATION OF AN MIBG ANALOG

The purpose of this study was to evaluate the properties of 4-fluoro-3 -[I-131]iodobenzylguanidine ([I-131]FIBG), a potential neuroendocrine tumor and myocardial imaging radiopharmaceutical. Methods: The binding of [I-131]FIBG and [I-125]MIBG was compared in vitro using the SK-N-S H human neuroblastoma cell line. The role of the active uptake-1 mecha nism was investigated by determining the effect on cell binding of des ipramine (DMI), ouabain, norepinephrine (NE), unlabeled MIBG and FIBG and by incubation at 4 degrees C. Finally, the tissue distributions of [I-131]FIBG and [I-125]MIBG were compared in normal mice. Results: Th e specific binding of [I-131]FIBG remained fairly constant (45%-60%) o ver a 2-3-log activity range and consistently was 11%-14% higher (p < 0.05) than that of [I-125]MIBG. The uptake of [I-131]FIBG was reduced to 13% of control values by 1.5 mu M DMI, to 31% by 1 mM ouabain, to 8 % by lower temperature, to 8% by 50 mu M NE and to 6% and 5% by 10 mu M each of unlabeled MIBG and FIBG, respectively. The amount of [I-131] FIBG retained by SK-N-SH cells was significantly higher than that of [ I-125]MIBG with the maximum difference observed at 72 hr. In mice, the uptake of [I-131]FIBG was higher than that of [I-125]MIBG not only in target tissues (heart and adrenals) but also in many other normal tis sues; conversely, thyroidal uptake of [I-131]FIBG was 2-3-fold lower t han that of [(125)]MIBG. The uptake of [I-131]FIBG in the heart and ad renals was reduced by DMI, Conclusion: Iodine-131-FIBG is an analog of MIBG with prolonged binding to neuroblastoma cells in vitro and reten tion in the myocardium in vivo.