Validation of Parametric Methods for [¹¹C]UCB-J PET Imaging Using Subcortical White Matter as Reference Tissue

Area of Science:

• Neuroimaging
• Radiochemistry
• Pharmacology

Background:

• Positron Emission Tomography (PET) enables non-invasive imaging of neurochemical targets.
• [11C]UCB-J is a PET tracer for synaptic vesicle glycoprotein 2A (SV2A), a target relevant to neurological disorders.
• Accurate quantification of tracer binding is crucial for clinical applications.

Purpose of the Study:

• To evaluate non-invasive methods for generating parametric maps of [11C]UCB-J binding potential.
• To compare different kinetic modeling techniques using white matter (centrum semi-ovale, SO) as reference tissue.
• To assess the impact of reduced scan durations on quantification accuracy.

Main Methods:

• Ten healthy volunteers underwent 90-minute dynamic [11C]UCB-J PET scans with arterial input function.
• Analyzed data using Simplified Reference Tissue Model 2 (SRTM2), Multilinear Reference Tissue Model 2 (MRTM2), and Reference Logan Graphical Analysis (rLGA).
• Compared parametric maps (BP_SO) and Standardized Uptake Value Ratios (SUVR_SO) against a 1-tissue compartment model (1TCM DVR_SO).

Main Results:

• All methods showed high correlations with 1TCM DVR_SO.
• SRTM2 and MRTM2 demonstrated low bias and variability for 90-minute scans, outperforming rLGA.
• Reducing scan time to 60 minutes had minimal impact on SRTM2 accuracy.
• Static SUVR_SO (60-90 min and 50-80 min) also showed low bias and variability.

Conclusions:

• SRTM2 is the preferred method for voxelwise analysis of dynamic [11C]UCB-J PET using SO reference tissue.
• A 60-minute acquisition is sufficient for generating reliable [11C]UCB-J BP_SO parametric maps.
• Static SUVR_SO images are effective proxies for parametric maps in static PET protocols.