Validation of 4-[fluorine-18]fluoro-3-iodobenzylguanidine as a positron-emitting analog of MIBG.

Abstract

This study evaluates the potential utility of 4-[18F]fluoro-3-iodobenzylguanidine ([18F]FIBG) as an MIBG analog. In vitro assays of tracer binding were carried out using the SK-N-SH human neuroblastoma cell line in a paired-label format to compare [18F]FIBG directly with no-carrier-added [125I]MIBG. To ascertain whether [18F]FIBG, like MIBG, is taken up by the uptake-1 mechanism, the effects of desipramine, norepinephrine, and carrier MIBG and FIBG on cell binding were determined. Preincubation with ouabain and incubation at 4 degrees C was used to evaluate the energy-dependence of [18F]FIBG uptake by SK-N-SH cells. The tissue distribution of [18F]FIBG in mice was compared with no-carrier-added [125I]MIBG in a paired-label study. In paired-label binding studies, the percent binding of [18F]FIBG to neuroblastoma cells remained constant over a three-log activity range and the level was somewhat higher than that of no-carrier-added [125I]MIBG. Binding was blocked by desipramine, norepinephrine, carrier MIBG and FIBG, ouabain and by incubating at 4 degrees C, suggesting that [18F]FIBG is taken up by the uptake-1 mechanism. Radiation dosimetry calculations suggest that higher doses of [18F]FIBG, unlike [124I]MIBG, could be administered to patients. These in vitro and in vivo evaluations show that [18F]FIBG is an excellent analog of MIBG, suggesting that [18F]FIBG should be further evaluated for use in PET imaging of neuroendocrine tumors and cardiac abnormalities.