Introduction9-[18 F]Fluoropropyl-(+)-dihydrotetrabenazine ([18 F]AV-133) is a new PET imaging agent targeting vesicular monoamine transporter type II (VMAT2). To shorten the preparation of [18 F]AV-133 and to make it more widely available, a simple and rapid purification method using solid-phase extraction (SPE) instead of high-pressure liquid chromatography (HPLC) was developed. The SPE method produced doses containing the non-radioactive pseudo-carrier 9-hydroxypropyl-(+)-dihydrotetrabenazine (AV-149). The objectives of this study were to evaluate the brain uptake of AV-149 by UPLC-MS/MS and its effect on the biodistribution of [18 F]AV-133 in the brains of mice.MethodsThe mice were injected with a bolus including [18 F]AV-133 and different doses of AV-149. Brain tissue and blood samples were harvested. The effect of different amounts of AV-149 on [18 F]AV-133 was evaluated by quantifying the brain distribution of radiolabelled tracer [18 F]AV-133. The concentrations of AV-149 in the brain and plasma were analyzed using a UPLC-MS/MS method.ResultsThe concentrations of AV-149 in the brain and plasma exhibited a good linear relationship with the doses. The receptor occupancy curve was fit, and the calculated ED50 value was 8.165 mg/kg. The brain biodistribution and regional selectivity of [18 F]AV-133 had no obvious differences at AV-149 doses lower than 0.1 mg/kg. With increasing doses of AV-149, the brain biodistribution of [18 F]AV-133 changed significantly.ConclusionThe results are important to further support that the improved radiolabelling procedure of [18 F]AV-133 using an SPE method may be suitable for routine clinical application.

Serotonin transporters (SERT) in the brain play an important role in normal brain function. Selective serotonin reuptake inhibitors such as fluoxetine, sertraline, paroxetine, escitalopram, etc., specifically target SERT binding in the brain. Development of SERT imaging agents may be useful for studying the function of SERT by in vivo imaging. A one-step preparation of [18F]FPBM, 2-(2′-(dimethylamino)methyl)-4′-(3-([18F]fluoropropoxy)phenylthio)benzenamine, for positron emission tomography (PET) imaging of SERT binding in the brain was achieved. An active OTs intermediate, 9, was reacted with [18F]F−/K222 to produce [18F]FPBM in one step and in high radiochemical yield. This labeling reaction was evaluated and optimized under different temperatures, bases, solvents, and varying amounts of precursor 9. The radiolabeling reaction led to the desired [18F]FPBM in one step and the crude product was purified by HPLC purification to give no-carrier-added [18F]FPBM (radiochemical yield, 24–33%, decay corrected; radiochemical purity > 99%). PET imaging studies in normal monkeys (n = 4) showed fast, pronounced uptakes in the midbrain and thalamus, regions known to be rich in SERT binding sites. A displacement experiment with escitalopram (5 mg/kg iv injection at 30 min after [18F]FPBM injection) showed a rapid and complete reversal of SERT binding, suggesting that binding by [18F]FPBM was highly specific and reversible. A one-step radiolabeling method coupled with HPLC purification for preparation of [18F]FPBM was developed. Imaging studies suggest that it is feasible to use this method to prepare [18F]FPBM for in vivo PET imaging of SERT binding in the brain.