Eur J Nucl Med Mol Imaging. 2015 Apr 2. [Epub ahead of print]
PURPOSE:Activated microglia play a key role in inflammatory demyelinating injury in multiple sclerosis (MS). Microglial activation can be measured in vivo using a positron emission tomography (PET) ligand 11C-PBR28. We evaluated the test-retest variability (TRV) and lesion detectability of 11C-PBR28 binding in MS subjects and healthy controls (HCs) with high-resolution PET.
METHODS: Four clinically and radiologically stable relapsing-remitting MS subjects (age 41 ± 7 years, two men/two women) and four HCs (age 42 ± 8 years, 2 two men/two women). Another MS subject (age 41 years, male) with clinical and radiological activity was studied for lesion detectability. Dynamic data were acquired over 120 min after injection of 634 ± 101 MBq 11C-PBR28. For the TRV study, subjects were scanned twice, on average 1.4 weeks apart. Volume of distribution (V T) was the main outcome measure.
RESULTS: Mean test V T values (ml cm-3) were 3.9 ± 1.4 in the whole brain gray matter (GM), 3.6 ± 1.2 in the whole brain white matter (WM) or normal-appearing white matter (NAWM), and 3.3 ± 0.6 in MS WM lesions; mean retest V T values were 3.7 ± 1.0 in GM, 3.3 ± 0.9 in WM/NAWM, and 3.3 ± 0.7 in MS lesions. Test-retest results showed a mean absolute TRV ranging from 7 to 9 % across GM, WM/NAWM, and MS lesions. Focal 11C-PBR28 uptake was detected in two enhancing lesions of the active MS patient.
CONCLUSION: High-resolution 11C-PBR28 PET can visualize focal areas where microglial activation is known to be present and has good test-retest reproducibility in the human brain. 11C-PBR28 PET is likely to be valuable for monitoring both MS disease evolution and response to therapeutic strategies that target microglial activation.