Imaging Microtubule Dynamics In Vivo in Human Brain: Optimal Quantification Based on a Test-Retest Study

Area of Science:

• Neuroscience
• Radiochemistry
• Medical Imaging

Background:

• Microtubules are crucial cytoskeletal components in the brain, essential for neuronal structure, transport, and cognitive functions.
• In vivo quantification of microtubule dynamics is achievable using Positron Emission Tomography (PET) with the radiotracer 11C-MPC6827.
• Previous evaluations of 11C-MPC6827 were conducted in animal models, necessitating human studies.

Purpose of the Study:

• To assess the test-retest properties of 11C-MPC6827 in healthy human subjects.
• To evaluate the impact of scan duration on the repeatability of 11C-MPC6827 PET imaging.
• To compare different quantification methods for microtubule dynamics using this radiotracer.

Main Methods:

• Five healthy volunteers underwent two 90-minute 11C-MPC6827 PET scans with arterial blood sampling.
• Total distribution volume (VT) was estimated using kinetic modeling and graphical analysis.
• Scan durations were truncated to 60 minutes to assess time stability, with repeatability measured by percent difference and intraclass correlation.

Main Results:

• VT estimates remained stable even with reduced scan times.
• Kinetic modeling showed test-retest percent differences between 10.18% and 14.26% for same-day scans.
• The SUV ratio to whole brain (SUVRWB) demonstrated higher stability (2.22%-5.47% TRPD) and was less affected by scan duration compared to SUV, though with lower ICCs than VT.

Conclusions:

• 11C-MPC6827 exhibits good repeatability for quantifying human brain microtubule dynamics, even with a 60-minute scan duration.
• Arterial blood sampling is effective for quantification.
• SUVRWB presents a practical, blood-free alternative for estimating microtubule dynamics.