Brain uptake of a non-radioactive pseudo-carrier and its effect on the biodistribution of [18F]AV-133 in mouse brain

Introduction: 9-[F-18]Fluoropropyl-(+)-dihydrotetrabenazine ([F-18]AV-133) is a new PET imaging agent targeting vesicular monoamine transporter type II (VMAT2). To shorten the preparation of [F-18]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 [F-18]AV-133 in the brains of mice. Methods: The mice were injected with a bolus including [F-18]AV-133 and different doses of AV-149. Brain tissue and blood samples were harvested. The effect of different amounts of AV-149 on [F-18]AV-133 was evaluated by quantifying the brain distribution of radiolabelled tracer [F-18]AV-133. The concentrations of AV-149 in the brain and plasma were analyzed using a UPLC-MS/MS method. Results: The 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 [F-18]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 [F-18]AV-133 changed significantly. Conclusion: The results are important to further support that the improved radiolabelling procedure of [F-18]AV-133 using an SPE method may be suitable for routine clinical application. (C) 2015 Elsevier Inc. All rights reserved.