Synthesis and regional mouse brain distribution of [11C]nisoxetine, a norepinephrine uptake inhibitor.

Nisoxetine, a selective and high affinity (IC50 = 1 nM) inhibitor of NE reuptake, has been radiolabeled in high specific activity (greater than 600 Ci/mmol) by the alkylation of the nor-methyl precursor with [11C]CH3I. Synthetic yields are good (40-60% from [11C]methyl iodide, corrected for decay, 20 min synthesis), with the product purified by HPLC. In vivo studies of regional brain distribution in CD-1 mice show uptake and retention of tracer in the cortex, striatum, hypothalamus and thalamus, with the highest levels in the hypothalamus and cortex. Specific binding in the cortex and hypothalamus can be reduced by preadministration of 7 mg/kg i.v. unlabeled nisoxetine. The possible value of [11C]nisoxetine as a PET imaging agent is discussed.