Florbenazine F18

[¹⁸F]fluoropropyl-(+)-dihydrotetrabenazine ([¹⁸F]FP-(+)-DTBZ) is a rising positron tracer for imaging vesicular monoamine transporter II (VMAT2) in the central nervous system. The present work was to develop a novel chromatographic method capable of the molar activity (A_m) determination of [¹⁸F]FP-(+)-DTBZ. As a complement work of the A_m measurement, we also investigated the effect of A_m on the quantitative analysis of VMAT2 autoradiography with [¹⁸F]FP-(+)-DTBZ. The A_m determination was performed by high performance liquid chromatography (HPLC) using the non-radioactive standard (FP-(+)-DTBZ) for calibration plot of peak area against concentration. Based on this correlation, the A_m of [¹⁸F]FP-(+)-DTBZ was calculated and corrected to the end of synthesis. In the quantitative analysis of in vitro VMAT2 autoradiography, the striatum radioactivity uptake together with the uptake ratio of striatum versus cortex reduced along with the decrease of A_m and the increase of the FP-(+)-DTBZ content. Therefore, the A_m and the corresponding FP-(+)-DTBZ content have a significant effect on the quantitative analysis of VMAT2 autoradiography using [¹⁸F]FP-(+)-DTBZ.

Background: Imaging biomarkers have the potential to distinguish between different brain pathologies based on the type of ligand used with PET. AV-45 PET (florbetapir, Amyvid™) is selective for the neuritic plaque amyloid of Alzheimer’s disease (AD), while AV-133 PET (florbenazine) is selective for VMAT2, which is a dopaminergic marker. Objective: To report the clinical, AV-133 PET, AV-45 PET, and neuropathological findings of three clinically diagnosed dementia patients who were part of the Avid Radiopharmaceuticals AV133-B03 study as well as the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND). Methods: Three subjects who had PET imaging with both AV-133 and AV-45 as well as a standardized neuropathological assessment were included. The final clinical, PET scan, and neuropathological diagnoses were compared. Results: The clinical and neuropathological diagnoses were made blinded to PET scan results. The first subject had a clinical diagnosis of dementia with Lewy bodies (DLB); AV-133 PET showed bilateral striatal dopaminergic degeneration, and AV-45 PET was positive for amyloid. The final clinicopathological diagnosis was DLB and AD. The second subject was diagnosed clinically with probable AD; AV-45 PET was positive for amyloid, while striatal AV-133 PET was normal. The final clinicopathological diagnosis was DLB and AD. The third subject had a clinical diagnosis of DLB. Her AV-45 PET was positive for amyloid and striatal AV-133 showed dopaminergic degeneration. The final clinicopathological diagnosis was multiple system atrophy and AD. Conclusion: PET imaging using AV-133 for the assessment of striatal VMAT2 density may help distinguish between AD and DLB. However, some cases of DLB with less-pronounced nigrostriatal dopaminergic neuronal loss may be missed.