VMAT2 imaging agent, D6-[¹⁸F]FP-(+)-DTBZ: Improved radiosynthesis, purification by solid-phase extraction and...

Area of Science:

• Nuclear Medicine
• Radiochemistry
• Neuroscience

Background:

• Parkinson's disease (PD) diagnosis relies on identifying neurodegeneration in the central nervous system.
• Vesicular monoamine transporter 2 (VMAT2) is a key biomarker for dopaminergic neurons affected in PD.
• Developing specific and efficient imaging agents for VMAT2 is crucial for early PD diagnosis.

Purpose of the Study:

• To optimize the production and purification of a deuterated VMAT2 tracer, D6-[¹⁸F]FP-(+)-DTBZ ([¹⁸F]9).
• To evaluate the efficacy of solid-phase extraction (SPE) for simplifying the purification process.
• To assess the impact of chemical impurities on the imaging agent's performance in vitro and in vivo.

Main Methods:

• Optimized radiolabeling conditions for [¹⁸F]9 synthesis, including temperature, time, and solvent.
• Developed and validated a solid-phase extraction (SPE) method using a C18 cartridge for purification.
• Assessed the influence of chemical impurities through in vitro binding assays, in vivo biodistribution studies in mice, and autoradiography.

Main Results:

• Optimized fluorination yielded high radiochemical yields (>99% purity) with reduced chemical impurities.
• An SPE method with a two-step elution provided efficient purification, comparable to HPLC.
• In vivo and ex vivo studies showed no significant difference in biodistribution between SPE- and HPLC-purified [¹⁸F]9.

Conclusions:

• The optimized production and SPE purification of [¹⁸F]9 offer a simplified, rapid, and effective method for preparing this VMAT2 imaging agent.
• The SPE-purified [¹⁸F]9 maintains high radiochemical purity and performance, suitable for clinical applications.
• This VMAT2 targeting agent holds promise as a valuable tool for Parkinson's disease diagnosis using PET imaging.