INCREASING THE POWER OF [18F]AV133 PET TO MEASURE LONGITUDINAL CHANGES IN PARKINSON’S DISEASE: IDENITIFICATION OF OPTIMAL REFERENCE AND TARGET REGIONS

Session Type
SYMPOSIUM
Date
Sat, 01.04.2023
Session Time
08:40 - 10:40
Room
ONSITE - HALL G3
Presenter
  • Zhen Fan (United Kingdom)
Lecture Time
08:40 - 08:55

Abstract

Aims

[18F]AV133 PET is a biomarker of nigral-striatal dopaminergic function that putatively measures reduced vesicular monoamine transporter (VMAT-2) density in progressing Parkinson’s disease. This study aimed to identify the optimal target and reference regions for quantifying [18F]AV133 so as to maximise power in future clinical imaging trials of novel therapies.

Methods

The Parkinson Progression Marker Initiative (PPMI) is a multicentre, international observational clinical study to assess PD biomarkers, including [18F]AV133 PET and Ioflupane (DaT). Longitudinal [18F]AV133 PET imaging data was available for 38 subjects, each of whom were followed for up to 4 years. Emission data were acquired for 10 mins between 80--90 post-injection of the tracer. Each subject had an associated T1 MRI which was used for inter-subject registration into stereotaxic space (MNI152). Data were quantified using an SUVR approach – permutations of five reference and six target regions were evaluated to determine maximal power of longitudinal signal change (S:N) (Fig1). [18F]AV133 data were also compared with the DaT data obtained from the same subjects.

fig1.longitudinal_analysis.jpg

Results

[18F]AV133 quantification using the cerebral white matter as the reference region and putamen as the target region showed the highest power (S:N = 1.1). [18F]AV133 showed a 75% and 71% increase in statistical power in year 1 and year 2 follow up when compared with DaT leading to a ~46% reduction in sample size required to detect the same pharmacodynamic changes (Fig2).

fig2.power_analysis.jpg

Conclusions

Cerebral white matter and putamen were selected as the optimal reference and target regions for [18F]AV133 quantification. With the limitation of small sample size, [18F]AV133 provides increased sensitivity to longitudinal changes in PD over existing DaT imaging, increasing power to detect pharmacodynamic responses and likely reduced sample sizes in future clinical imaging trials.

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