VMAT2 imaging agent, D6-[F]FP-(+)-DTBZ: Improved radiosynthesis, purification by solid-phase extraction and characterization.

OBJECTIVES

Recently, a deuterated tracer, D6-[F]FP-(+)-DTBZ, 9-O-hexadeutero-3-[F]fluoropropoxyl-(+)-dihydrotetrabenazine ([F]9), targeting vesicular monoamine transporter 2 (VMAT2) in the central nervous system, was reported as a useful imaging agent for the diagnosis of Parkinson's disease (PD). The production of [F]9 was optimized and simplified by using solid-phase extraction (SPE) purification.

METHODS

Three major nonradioactive impurities were synthesized and characterized. The preparation of [F]9 was optimized by using different labeling conditions, and an SPE purification method was evaluated. The influence of chemical impurities in the final dose of [F]9 was assessed by an in vitro binding assay, an assay of the in vivo biodistribution in mice, and ex vivo and in vitro autoradiography of brain sections.

RESULTS

Optimized fluorination conditions for [F]9 were found - heating at 130 °C for 10 min in DMSO, and a high radiochemical yield and three major chemical impurities were observed. An SPE method involving a Sep-Pak® tC18 Plus Light cartridge with a two-step elution process was successfully implemented. This process gave a good radiochemical yield (38.7 ± 10.5%, decay corrected; radiochemical purity >99%) and low chemical impurities. An in vivo biodistribution study and autoradiography of brain sections showed that there was no significant difference between HPLC-purified and SPE-purified [F]9.

CONCLUSION

A VMAT2 targeting imaging agent, D6-[F]FP-(+)-DTBZ, [F]9, was prepared by optimized labeling conditions and an easy SPE purification. This method offers a short preparation time and operational simplicity. In conjunction with PET imaging, this new VMAT2 agent might be a useful clinical tool for diagnosing PD.