Noninvasive Quantification of [¹⁸F]SynVesT-2 PET in Healthy Human Brains Using Simplified Reference Tissue Models.

Area of Science:

• Neuroimaging
• Radiochemistry
• Neurology

Background:

• Positron emission tomography (PET) imaging of synaptic vesicle glycoprotein 2A (SV2A) is crucial for studying neurologic disorders.
• Dynamic SV2A PET scans assess cerebral blood flow and SV2A density, both altered in conditions like Alzheimer disease.
• [18F]SynVesT-2 exhibits rapid brain kinetics and high specific binding, making it a promising SV2A PET tracer.

Purpose of the Study:

• To evaluate simplified reference tissue models (SRTMs) for quantifying [18F]SynVesT-2 PET data.
• To determine the minimum scan times for reliable estimation of relative cerebral blood flow and SV2A density using [18F]SynVesT-2.
• To enhance the clinical feasibility of dynamic SV2A PET imaging.

Main Methods:

• Data from 14 [18F]SynVesT-2 PET scans in 9 healthy volunteers were analyzed.
• Three SRTMs (SRTM, SRTMC, SRTM2) were applied using centrum semiovale and cerebellum as reference regions.
• Test-retest variability (TRV) and minimum scan durations for estimating R1, BPND, and DVR were evaluated.

Main Results:

• SRTM2 provided reliable nondisplaceable binding potential (BPND) and distribution volume ratio (DVR) estimates.
• BPND and DVR values converged after 40 minutes using SRTM2.
• A 40-minute dynamic scan with SRTM2 demonstrated low test-retest variability for BPND and DVR.

Conclusions:

• Relative cerebral blood flow (R1) and specific binding (BPND, DVR) can be reliably estimated from a 40-minute [18F]SynVesT-2 PET scan using SRTM2.
• This 40-minute protocol is significantly shorter than previous methods, improving clinical feasibility.
• The shortened scan time facilitates the clinical application of dynamic SV2A PET for maximizing diagnostic information.