In vivo evaluation of a microtubule PET ligand, [C]MPC-6827, in mice following chronic alcohol consumption.

Background: Excessive alcohol consumption is a global health burden and requires a better understanding of its neurobiology. A lower density of brain microtubules is found in alcohol-related human brain disease postmortem and in rodent models of chronic alcohol consumption. Here, we report in vivo imaging studies of microtubules in brain using our recently reported Positron Emission Tomography (PET) tracer, [C]MPC-6827, in chronic alcohol-consuming adult male C57BL/6 J mice and control mice.

Methods: In vivo PET imaging studies of [C]MPC-6827 (3.7  ±  0.8 MBq) were performed in two groups of adult male mice: (1) water-consuming control mice (n  =  4) and (2) mice that consumed 20% alcohol (w/v) for 4 months using the intermittent 2-bottle choice procedure that has been shown to lead to signs of alcohol dependence. Dynamic 63 min PET images were acquired using a microPET Inveon system (Siemens, Germany). PET images were reconstructed using the 3D-OSEM algorithm and analyzed using VivoQuant version 4 (Invicro, MA). Tracer uptake in ROIs that included whole brain, prefrontal cortex (PFC), liver and heart was measured and plotted as %ID/g over time (0-63 min) to generate time-activity curves (TACs).

Results: In general, a trend for lower binding of [C]MPC-6827 in the whole brain and PFC of mice in the chronic alcohol group was found compared with control group. No group difference in radiotracer binding was found in the peripheral organs such as liver and heart.

Conclusions: This pilot study indicates a trend of loss of microtubule binding in whole brain and prefrontal cortex of chronic alcohol administered mice brain compared to control mice, but no loss in heart or liver. These results indicate the potential of [C]MPC-6827 as a PET ligand for further in vivo imaging investigations of AUD in human.