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

Microtubules are cytoskeletal components that play essential roles in the brain, including supporting neuronal structure, protein transport, and cognitive function. In vivo quantification of microtubule dynamics using PET is possible with ¹¹C-MPC6827, a brain-penetrant radiotracer that has been evaluated in mice and nonhuman primates. Here we present the first assessment of ¹¹C-MPC6827 test-retest properties in a healthy human brain and examine the influence of scan duration on repeatability. Methods: Five healthy volunteers underwent two 90-min ¹¹C-MPC6827 PET scans with concurrent arterial blood sampling (4 imaged twice in 1 d, 1 rescanned after 1 y). Radiotracer time-activity curves were extracted from 46 individual brain regions, in addition to the whole brain. Total distribution volume (V _T) was estimated using kinetic models and graphical analysis. SUVs and the SUV ratio to whole brain (SUVR_WB) were computed in 2 postinjection time windows. Repeatability was assessed using absolute test-retest percent difference (TRPD) and intraclass correlation coefficient (ICC). Time stability was examined by truncating imaging data from 90-min to 60-min acquisition and comparing computed outcomes to the 90-min value as gold standard. Results: V _T estimates were stable with truncated scan time (average shorter V _T/90-min V _T, 1.003-1.030). For the same-day test-retest pairs, V _T estimates obtained with kinetic models showed average TRPD values, across regions and participants, between 10.18% and 14.26%, and ICCs between 0.483 and 0.966. Graphical approaches demonstrated lower repeatability than kinetic models. Across methods, TRPDs were lower and ICCs were higher with shorter scans. SUV showed higher interscan variability in TRPD. SUVR_WB was more stable (TRPD, 2.22%-5.47%) and less influenced by scan duration. However, ICCs were overall much lower for SUV and SUVR_WB than for V _T Conclusion: ¹¹C-MPC6827 shows good repeatability for quantifying microtubule dynamics in humans using arterial blood even at a 60-min scan duration. SUVR_WB could be a convenient blood-free alternative to V _T.