Effect of anesthesia agents on [123I]MIBG transport in neuroblastoma cells and biodistribution in mice

1579 Objectives: Small animal imaging is providing a unique opportunity to investigate the in vivo handling of various radioprobes, which includes [123I]MIBG imaging of neuroendocrine tumors, adrenals and myocardium. The use of anesthetic agents, which is a prerequisite for animal imaging, has been suggested to affect norepinephrine (NE) transport. We thus investigated the effects of ketamine, xylazine and pentobarbital on [123I]MIBG transport in cultured neuroblastoma cells and [123I]MIBG biodistribution in mice. Methods: Human neuroblastoma SK-N-SH cells were treated with 100 or 300 μM ketamine (Ke), xylazine (Xy), ketamine plus xylazine (Ke/Xy), or pentobarbital (Pb) for either 2 or 4 hr and measured for 30 min [123I]MIBG uptake. Cells exposed for 2 hr with 300 μM anesthetics were evaluated for levels of NE transporters by western blot. Normal ICR mice were injected with Ke/Xy (100 and 8 mg/kg), Pb (50 mg/kg), or normal saline 15 min prior to injection of 1.85 MBq [123I]MIBG. Animals were euthanized 30 min later and major organs were measured for radiouptake. Results: In cultured SK-N-SH cells, Ke, Xy and Ke/Xy reduced [123I]MIBG uptake to 60.3±4.5%, 40.7±0.8% and 32.1±1.9% of controls at 2 hr and to 59.4±2.1%, 37.0±0.9%, and 39.6±5.9% of controls at 6 hr, respectively. In contrast, Pb had no affect on cellular [123I]MIBG uptake. Western blot showed that none of the anesthetic agents had an effect on NE transporter expression. In mice, Pb significantly decrease blood [123I]MIBG activity compared to controls (0.5±0.1 vs. 1.1±0.5 %ID/g, p Conclusions: Ke/Xy inhibits [123I]MIBG transport most likely through blocking of NE transporter sites, and leads to decreased blood and muscle activity with increased renal activity of [123I]MIBG in mice. Pb does not directly block [123I]MIBG transport, but also results in decreased blood and muscle activity, increased renal activity, and reduced myocardial uptake. These results demonstrate that the choice of anesthetics are important factors that affect [123I]MIBG transport and distribution in living animals.